Search

Summary Methyl-CpG binding protein 2 (MeCP2) has historically been linked to heterochromatin organization, and in mouse cells it accumulates at pericentric heterochromatin (PCH), closely following major satellite (MajSat) DNA distribution. However, little is known about the specific function of MeCP2 in these regions. We describe the first evidence of a role in neurons for MeCP2 and MajSat forward (MajSat-fw) RNA in reciprocal targeting to PCH through their physical interaction. Moreover, MeCP2 contributes to maintenance of PCH by promoting deposition of H3K9me3 and H4K20me3. We highlight that the MeCP2B isoform is required for correct higher-order PCH organization, and underline involvement of the methyl-binding and transcriptional repression domains. The T158 residue, which is commonly mutated in Rett patients, is directly involved in this process. Our findings support the hypothesis that MeCP2 and the MajSat-fw transcript are mutually dependent for PCH organization, and contribute to clarify MeCP2 function in the regulation of chromatin architecture., Graphical Abstract, Highlights • MeCP2 and MajSat-fw transcript targeting to chromocenters is mutually dependent • MeCP2B and its MBD domain are required for correct higher-order PCH organization • The TRD domain of the MeCP2 protein binds the MajSat-fw transcript • The Rett syndrome T158M mutation of MeCP2 impairs higher-order PCH organization, Della Ragione and colleagues describe a novel function of MeCP2 and MajSat forward transcript in terms of their reciprocal targeting to chromocenters in neurons through their physical interaction. Moreover, MeCP2B has a prominent role in higher-order PCH organization, with both its MBD and TRD involved in this process. These findings further clarify MeCP2 function in the regulation of chromatin architecture.

Summary Muscle satellite cells are normally quiescent but are rapidly activated following muscle damage. Here, we investigated whether damaged myofibers influence the activation of satellite cells. Our findings revealed that satellite cells are directly activated by damaged-myofiber-derived factors (DMDFs). DMDFs induced satellite cells to enter the cell cycle; however, the cells stayed at the G1 phase and did not undergo S phase, and these cells were reversible to the quiescent-like state. Proteome analysis identified metabolic enzymes, including GAPDH, as DMDFs, whose recombinant proteins stimulated the activation of satellite cells. Satellite cells pre-exposed to the DMDFs demonstrated accelerated proliferation ex vivo. Treatment with recombinant GAPDH prior to muscle injury promoted expansion of the satellite cell population in vivo. Thus, our results indicate that DMDFs are not only a set of biomarkers for muscle damage, but also act as moonlighting proteins involved in satellite cell activation at the initial step of muscle regeneration., Graphical Abstract, Highlights • Damaged-myofiber-derived factors (DMDFs) activate satellite cells • DMDFs induce activation, but not proliferation, of satellite cells • Satellite cells activated by DMDFs are reversible to the quiescent-like state • DMDFs play an important role in the initial step of muscle regeneration, In this article, Tsuchiya et al. demonstrate that muscle satellite cells are directly activated by damaged-myofiber-derived factors (DMDFs). DMDFs promote population expansion of satellite cells during muscle regeneration. DMDFs are not only a set of biomarkers for muscle damage, but also act as functional proteins involved in satellite cell activation at the initial step of muscle regeneration.

Pig is an important economic animal in China. Improving meat quality and meat productivity is a long time issue in animal genetic breeding. MicroRNAs (miRNAs) are short non-coding RNAs that participate in various biological processes, such as muscle development and embryogenesis. miR-22 differentially expresses in embryonic and adult skeletal muscle. However, the underlying mechanism is unclear. In this study, we investigated miR-22 function in proliferation and differentiation of porcine satellite cells (PSCs) in skeletal muscle. Our data show that miR-22 expressed in both proliferation and differentiated PSCs and is significantly upregulated (P

Our recent ability to sequence entire genomes, along with all of their transcribed RNAs, has led to the surprising finding that only ∼1% of the human genome is used to encode proteins. This finding has led to vigorous debate over the functional importance of the transcribed but untranslated portions of the genome. Currently, scientists tend to assume coding genes are functional until proven not to be, while the opposite is true for noncoding genes. This review takes a new look at the evidence for and against widespread noncoding gene functionality. We focus in particular on long noncoding RNA (noncoding RNAs longer than 200 nucleotides) genes and their 'junk' associates, transposable elements, and satellite repeats. Taken together, the suggestion put forward is that more of this junk DNA may be functional than nonfunctional and that noncoding RNAs and transposable elements act symbiotically to drive evolution.

Tobacco curly shoot virus (TbCSV) is a monopartite DNA virus of the genus Begomovirus, which causes leaf curl symptoms in tobacco and tomato. The β satellite of TbCSV (TbCSB induces more severe symptoms and enhanced virus accumulation when co-infects the host plants with TbCSV. Small interfering RNAs derived from virus(vsiRNAs) induce disease symptoms and promote virus invasion by target and guide the degradation of host transcripts The vsiRNAs derived from TbCSV and TbCSV + TbCSB remained to be explored to elucidate the molecular mechanism of symptoms development in plants. In the present work, two libraries of small RNA from TbCSV-infected and TbCSV + TbCSB-infected N. benthamiana plants were constructed and the vsiRNAs in both samples shared the same characteristics. The size of the vsiRNAs ranged from 18 to 30 nucleotides (nt), with most of them being 21 or 22 nt, which accounted for 29.11% and 23.22% in TbCSV plants and 29.39% and 21.82% in TbCSV + TbCSV plants, respectively. The vsiRNAs with A/U bias at the first site were abundant in both the TbCSV-treated and TbCSV + TbCSB-treated plants. It is discovered that the vsiRNAs continuously, but heterogeneously, distributed through bothe the TbCSV and TbCSB sequences. And the distribution profiles were similar in both the treatments such as mainly in the overlapping region of the AC2/AC3 coding sequences. The host transcripts targeted by vsiRNAs were predicted, and the targeted genes were found to be involved in varied biological processes. It is indicated that the presence of TbCSB does not significantly affect the production of vsiRNAs from TbCSV in plants, the distribution hotsopt of TbCSV vsiRNAs could be useful in designing effective targets for TbCSV resistance exploiting RNA interference.

Many fungal viruses or mycoviruses have multi-segmented, rather than single-segmented, genomes. This multi-segment nature is frequently possessed by double-stranded RNA viruses, which include members of the Chrysoviridae, Quadriviridae, Megabirnaviridae, Partitiviridae, and Reoviridae families, and unassigned groups. Their genome segments are often packaged separately with the exception of mycoreoviruses, which are multi-segmented but mono-particulate viruses. These multi-segmented fungal dsRNA viruses, as exemplified by reoviruses, have been extensively studied among structural biologists, and contributed to discoveries of novel virion structures. Multi-component systems, interactions of viruses with subviral agents such as satellite and defective RNAs as typified by the yeast killer, and the rule-breaking neo-virus lifestyle exhibited by a capsidless single-stranded RNA virus hosted in an unrelated double-stranded RNA virus are also discussed. Fungal multi-segmented viruses and multicomponent virus systems would continue to provide virologists with interesting future challenges.

Summary Adult muscle stem cells (satellite cells) are required for adult skeletal muscle regeneration. A proper balance between quiescence, proliferation, and differentiation is essential for the maintenance of the satellite cell pool and their regenerative function. Although the ubiquitin-proteasome is required for most protein degradation in mammalian cells, how its dysfunction affects tissue stem cells remains unclear. Here, we investigated the function of the proteasome in satellite cells using mice lacking the crucial proteasomal component, Rpt3. Ablation of Rpt3 in satellite cells decreased proteasome activity. Proteasome dysfunction in Rpt3-deficient satellite cells impaired their ability to proliferate, survive and differentiate, resulting in defective muscle regeneration. We found that inactivation of proteasomal activity induced proliferation defects and apoptosis in satellite cells. Mechanistically, insufficient proteasomal activity upregulated the p53 pathway, which caused cell-cycle arrest. Our findings delineate a critical function of the proteasome system in maintaining satellite cells in adult muscle., Graphical Abstract, Highlights • Ablation of Rpt3 in satellite cells leads to decreased proteasome activity • Proteasome dysfunction in satellite cells results in defective muscle regeneration • Proteasome dysfunction induces proliferation defects and apoptosis • Inhibition of p53 rescues Rpt3-mediated defects in proliferation, It is not clear how proteasome insufficiency affects tissue stem cells. Kitajima et al. demonstrate that the proteasome system is indispensable for the maintenance of muscle stem cells. Proteasome dysfunction in Rpt3-deficient satellite cells impairs their ability to proliferate, survive and differentiate, resulting in defective muscle regeneration.

Here, for the first time, we analyzed skeletal muscle morphology in Boer and Nanjiang Brown (NJ) goats and then evaluated the differences in skeletal muscle satellite cells (SMSCs) proliferation and differentiation ability between the two breeds. Our results revealed that NJ goats had significantly more myofiber cells and a significantly smaller cross-section area compared with the Boer goats (P

This study describes a new mycovirus infecting a strain from the Fusarium incarnatum-equiseti species complex. Based on phylogenetic and genomic analyses, this virus belongs to the recently proposed genus "Zetapartitivirus" in the family Partitiviridae. The name "Fusarium equiseti partitivirus 1″ (FePV1) is therefore suggested for this novel viral species. Similar to other partitiviruses, FePV1 genome is composed by two dsRNA segments that exhibit each one large ORF encoding for an RdRp and a CP, respectively. A smaller dsRNA was also detected in infected mycelium and could be a satellite RNA of FePV1. In addition to characterized zetapartitiviruses, other FePV1-related sequences were retrieved from online databases and their significance is discussed. Following conidial isolation, an FePV1-free isogenic line of the fungal host was obtained. In comparison with the original infected strain, this line showed higher growth, biomass production and pathogenicity on tomato, advocating that FePV1 induces hypovirulence on its host.

Satellite glia are the major glial type found in sympathetic and sensory ganglia in the peripheral nervous system, and specifically, contact neuronal cell bodies. Sympathetic and sensory neurons differ in morphological, molecular, and electrophysiological properties. However, the molecular diversity of the associated satellite glial cells remains unclear. Here, using single-cell RNA sequencing analysis, we identify five different populations of satellite glia from sympathetic and sensory ganglia. We define three shared populations of satellite glia enriched in immune-response genes, immediate-early genes, and ion channels/ECM-interactors, respectively. Sensory- and sympathetic-specific satellite glia are differentially enriched for modulators of lipid synthesis and metabolism. Sensory glia are also specifically enriched for genes involved in glutamate turnover. Furthermore, satellite glia and Schwann cells can be distinguished by unique transcriptional signatures. This study reveals the remarkable heterogeneity of satellite glia in the peripheral nervous system.

Noncoding RNAs use their sequence and/or structure to mediate function(s). The 5’ portion (166 nt) of the 356-nt noncoding satellite RNA C (satC) of Turnip crinkle virus (TCV) was previously modeled to contain a central region with two stem-loops (H6 and H7) and a large connecting hairpin (H2). We now report that in vivo functional selection (SELEX) experiments assessing sequence/structure requirements in H2, H6, and H7 reveal that H6 loop sequence motifs were recovered at nonrandom rates and only some residues are proposed to base-pair with accessible complementary sequences within the 5’ central region. In vitro SHAPE of SELEX winners indicates that the central region is heavily base-paired, such that along with the lower stem and H2 region, one extensive hairpin exists composing the entire 5’ region. As these SELEX winners are highly fit, these characteristics facilitate satRNA amplification in association with TCV in plants.

Neuropeptide Y (NPY) is an appetite stimulating peptide released from the central nervous system and impacts the function of many different cell types. A recent transcriptome study showed that NPY expression was altered when turkey breast muscle satellite cells were incubated at low or high temperatures, suggesting NPY may mediate temperature effects on satellite cells. However, to date minimal information exists describing the expression and function of NPY in satellite cells. The objective of this study was to determine how temperature impacts NPY and NPY receptor gene expression in satellite cells isolated from turkeys and chickens with differing genetic lineages. Two broiler and two turkey breast muscle satellite cell lines were incubated at 35, 38 or 41 °C during proliferation and differentiation. In both turkey lines, NPY, and receptors NPY2R and NPY5R expression increased at elevated temperatures after 72 h of proliferation. During differentiation NPY and NPY5R expression increased in both turkey lines with higher temperatures, whereas NPY2R was minimally affected by temperature. In contrast, in both chicken cell lines there were few significant differences for NPY and NPY receptor expression across temperature during proliferation. During differentiation, the temperature effect was different in the two chicken cell lines. In the BPM8 chicken line, there were few differences in NPY and NPY receptors across temperature; whereas elevated temperatures increased NPY, NPY2R, and NPY5R expression in the 708 line. The differences between turkey and chicken lines suggest NPY has species specific satellite cell functions in response to heat stress.

Summary Satellite cells function as precursor cells in mature skeletal muscle homeostasis and regeneration. In healthy tissue, these cells are maintained in a state of quiescence by a microenvironment formed by myofibers and basement membrane in which LAMININs (LMs) form a major component. In the present study, we evaluated the satellite cell microenvironment in vivo and found that these cells are encapsulated by LMα2–5. We sought to recapitulate this satellite cell niche in vitro by culturing satellite cells in the presence of recombinant LM-E8 fragments. We show that treatment with LM-E8 promotes proliferation of satellite cells in an undifferentiated state, through reduced phosphorylation of JNK and p38. On transplantation into injured muscle tissue, satellite cells cultured with LM-E8 promoted the regeneration of skeletal muscle. These findings represent an efficient method of culturing satellite cells for use in transplantation through the recapitulation of the satellite cell niche using recombinant LM-E8 fragments., Graphical Abstract, Highlights • Satellite cells are encapsulated by LMα2–5 • LM-E8 promotes proliferation of satellite cells in an undifferentiated state • Satellite cells cultured with LM-E8 enhanced the regeneration of skeletal muscle, In this study, examination of the satellite cell microenvironment in vivo revealed that these cells are encapsulated by LMα2–5. We find that reconstitution of the satellite cell niche with recombinant LM-E8 fragments promotes the proliferation and maintains satellite cells in an undifferentiated state.

Cortisol is a ubiquitously expressed stress hormone. In this study, we investigated the effects of exogenous cortisol on porcine gluteal muscles primary cultured satellite cells and fibroblasts. Satellite cells and fibroblasts were mono-or co-cultured, and cells in each type of culture were categorized into the control and cortisol-treated (treatment) groups. We selected 28 μmol mL−1 cortisol for treatment based on their efficacy. Cortisol treatment reduced viability of monocultured satellite cells and fibroblasts. In both monocultured and co-cultured cells, the nucleus in the treatment group was damaged than that control group. Moreover, the total cell cycle duration was shorter in the treatment group than the control group. PAX-7 expression was upregulated in the control group of co-cultured satellite cells and fibroblasts than those remaining groups. Moreover, MyoD expression was downregulated in the cortisol treated group of both mono-and co-cultured satellite cells compared with that in the control group. In co-cultured fibroblasts, MyoD and MyoG expression was upregulated than those remaining groups. The Cyto-C expression was upregulated in the treatment group compared to the control mono-and co-cultured both cells. These results suggest that the selected experimental dose of cortisol reduced cell viability and myogenesis-related gene expression in the monoculture compared to that in the co-culture of satellite cells and fibroblasts.

Satellite cells represent the main myogenic population accounting for skeletal muscle homeostasis and regeneration. While our knowledge of the signaling pathways controlling satellite cell regenerative capability is increasing, the underlying epigenetic mechanisms are still not clear, especially in the case of human satellite cells. Here, by performing chromatin accessibility profiling (ATAC-seq) in samples isolated from human and murine muscles, we investigated the changes in the epigenetic landscape occurring during the transition from activated satellite cells to myoblasts. Our analysis identifies a compendium of putative regulatory elements defining human activated satellite cells and myoblasts, respectively. A subset of these differentially accessible loci is shared by both murine and human satellite cells, includes elements associated with known self-renewal regulators, and is enriched for motifs bound by transcription factors participating in satellite cell regulation. Integration of transcriptional and epigenetic data reveals that known regulators of metabolic gene expression, such as PPARGC1A, represent potential PAX7 targets. Through characterization of genomic networks and the underlying effectors, our data represent an important starting point for decoding and manipulating the molecular mechanisms underlying human satellite cell muscle regenerative potential.

Summary Using in vivo muscle stem cell (satellite cell)-specific extracellular vesicle (EV) tracking, satellite cell depletion, in vitro cell culture, and single-cell RNA sequencing, we show satellite cells communicate with other cells in skeletal muscle during mechanical overload. Early satellite cell EV communication primes the muscle milieu for proper long-term extracellular matrix (ECM) deposition and is sufficient to support sustained hypertrophy in adult mice, even in the absence of fusion to muscle fibers. Satellite cells modulate chemokine gene expression across cell types within the first few days of loading, and EV delivery of miR-206 to fibrogenic cells represses Wisp1 expression required for appropriate ECM remodeling. Late-stage communication from myogenic cells during loading is widespread but may be targeted toward endothelial cells. Satellite cells coordinate adaptation by influencing the phenotype of recipient cells, which extends our understanding of their role in muscle adaptation beyond regeneration and myonuclear donation., Graphical abstract, Highlights • Widespread myogenic cell communication in muscle during mechanical overload (MOV) • Extracellular vesicles from myogenic progenitors repress Wisp1 in fibrogenic cells • Fibrogenic fate and chemokines are influenced by satellite cells early during MOV • Prior to fusion, satellite cell communication regulates long-term hypertrophy, Cell Biology; Functional Aspects of Cell Biology

Routinely in many laboratories, satellite rats are added to embryo-fetal development (EFD) studies for pharmaceuticals to assess toxicokinetic (TK) properties, because it is assumed that collection of multiple blood samples with relatively large volumes might affect the study outcome. With recent refinement of blood sampling techniques, this belief requires reevaluation. The current work showed successful implementation of jugular vein blood sampling in an EFD rat study without satellite animals, thereby reducing the number of rats in standard EFD studies for pharmaceuticals by 20%. Although not evaluated in this study, microsampling has shown to be very successful and eliminates the need of satellite animals. However, currently not all laboratories have implemented this method and regularly the bioanalytical method is already developed with a limit of quantification that is insufficiently sensitive. Therefore in those cases, a quick win to omit satellite animals can be established by using jugular vein blood sampling.

Sodium taurocholate cotransporting polypeptide (NTCP) is the functional receptor for human hepatitis B virus (HBV) and its satellite hepatitis D virus (HDV). Species barriers to HBV/HDV infection are mainly determined at entry level by variations in the sequences of particular NTCP orthologs. In this study, we sought to determine whether the NTCP ortholog in woodchuck (Marmota monax), woodchuck NTCP (wNTCP) supports viral infection. We found that wNTCP is capable of supporting HBV/HDV infection in HepG2 cells, but to much lower extent than human NTCP (hNTCP), which is about 90% reduction of hNTCP. Comprehensive site-directed mutagenesis mapping of hNTCP and wNTCP revealed that the residue at position 263 is a novel site crucial for viral entry. The important role of site 263 in infection is conserved among NTCP orthologs and may therefore be a potential target for blocking the viral entry.

Immature poults have an inefficient thermoregulatory system, and therefore extreme ambient temperatures can impact their internal body temperature. Satellite cells, the only posthatch myonuclei source, are multipotential stem cells and sensitive to temperature. Selection for faster-growing, high-yielding birds has altered satellite-cell properties. The objective of the current study was to determine how temperature affects adipogenic properties of satellite cells isolated from the pectoralis major ( ) muscle of Randombred Control line ( ) and F line turkeys selected only for increased 16-wk body weight from the RBC2 line. Satellite cells were cultured at 2°C incremental temperatures between 33 and 43°C and compared to cells cultured at the control temperature of 38°C to ascertain temperature effects on lipid accumulation and expression of adipogenic genes: CCAAT/enhancer-binding protein-β ( ), peroxisome proliferator-activated receptor-γ ( ), and stearoyl-CoA desaturase ( ). During proliferation, the amount of quantifiable lipid in both F and RBC2 satellite cells increased at temperatures above 38°C ( P 0.01) and decreased at temperatures below 38°C ( P 0.01). Above 38°C, RBC2 satellite cells had more lipid ( P = 0.02) compared to the F line, whereas there were few differences between lines below 38°C. At 72 h of proliferation, expression of C/EBPβ , PPARγ , and SCD decreased ( P ≤ 0.02) as temperatures increased from 33 to 43°C in both cell lines. During differentiation expression of C/EBPβ increased ( P 0.01) as temperatures increased from 33 to 43°C in both cell lines. In F line satellite cells, PPARγ expression decreased ( P 0.01) with increasing temperatures during differentiation, whereas there was no linear trend in RBC2 cells. During differentiation expression of SCD increased as temperatures increased ( P 0.01) in RBC2 cells, and there was no linear trend within the F line. Results from the current study suggest that environmental temperature can affect p. major satellite cellular fate; however, selection for increased body weight had little impact on these cellular responses.

Muscle satellite cells can proliferate and differentiate into myocytes; this biological function has important implications for muscle development, aging, repair, and wasting diseases. Established analytical methods, including western blotting, PCR, and immunohistochemistry, has been used to characterize the stages of satellite cells growth and development but there is currently a lack of methods to simultaneously monitor cell proliferation and identify changes in cell properties (i.e., expression of myogenic regulatory factors) for each individual cell during the progression to become myocytes. Image-based flow cytometry has the capability to simultaneously obtain morphometric data, monitor cell division, and detect expression of multiple proteins of interest. In this article we demonstrate the use of image-based flow cytometry and cell-trace dye to monitor satellite cells proliferation and to identify different stages of satellite cell differentiation.

Female meiosis provides an opportunity for selfish genetic elements to violate Mendel's law of segregation by increasing the chance of segregating to the egg [1]. Centromeres and other repetitive sequences can drive in meiosis by cheating the segregation process [2], but the underlying mechanisms are unknown. Here, we show that centromeres with more satellite repeats house more nucleosomes that confer centromere identity, containing the histone H3 variant CENP-A, and bias their segregation to the egg relative to centromeres with fewer repeats. CENP-A nucleosomes predominantly occupy a single site within the repeating unit that becomes limiting for centromere assembly on smaller centromeres. We propose that amplified repetitive sequences act as selfish elements by promoting expansion of CENP-A chromatin and increased transmission through the female germline.

Geminiviruses constitute one of the largest groups of plant viruses, having characteristic twinned geminate particles encapsidating small circular single-stranded DNA molecules. Geminiviral promoters are generally located within the intergenic region, although promoters have also been detected within the genes. Similarly, the geminivirus-associated betasatellite also harbours a promoter element for driving the expression of its only ORF. These regulatory elements of geminiviral and satellite origins have been subject of great interest to develop heterologous gene expression modules. Geminiviral promoter and regulatory elements show a complex regulation that is mediated by several host as well as viral proteins. Here, the structural and functional features of geminiviral and satellite promoters are discussed along with their regulation by plant and viral proteins. Although generalization in many cases is difficult and demands further studies, a pattern is seen to emerge on the regulation of the promoters.

Recent findings employing the mdx mouse model for Duchenne muscular dystrophy (DMD) have revealed that muscle satellite stem cells play a direct role in contributing to disease etiology and progression of DMD, the most common and severe form of muscular dystrophy. Lack of dystrophin expression in DMD has critical consequences in satellite cells including an inability to establish cell polarity, abrogation of asymmetric satellite stem cell divisions and failure to enter the myogenic program. Thus, muscle wasting in dystrophic mice is not only caused by myofiber fragility, but is exacerbated by intrinsic satellite cell dysfunction leading to impaired regeneration. Despite intense research and clinical efforts, there is still no effective cure for DMD. In this review, we highlight recent research advances in DMD and discuss the current state of treatment and importantly, how we can incorporate satellite cell-targeted therapeutic strategies to correct satellite cell dysfunction in DMD.

Summary Regeneration of vertebrate skeletal muscles requires satellite cells, a population of stem cells that are quiescent in normal conditions and divide, differentiate, and self-renew upon activation triggered by exercise, injury, and degenerative diseases. Satellite cell self-renewal is essential for long-term tissue homeostasis, and previous work has identified a number of external cues that control this process. However, little is known of the possible intrinsic control mechanisms of satellite cell self-renewal. Here, we show that quiescent satellite cells harbor a primary cilium, which is rapidly disassembled upon entry into the cell cycle. Contrasting with a commonly accepted belief, cilia reassembly does not occur uniformly in cells exiting the cell cycle. We found that primary cilia reassemble preferentially in cells committed to self-renew, and disruption of cilia reassembly causes a specific deficit in self-renewing satellite cells. These observations indicate that primary cilia provide an intrinsic cue essential for satellite cell self-renewal., Highlights • In skeletal muscles, primary cilia are associated with quiescent satellite cells • Primary cilia disassemble when satellite cells enter the cell cycle • Primary cilia reassemble preferentially in self-renewing satellite cells • Disruption of primary cilia reassembly impairs satellite cell self-renewal, In this article, Borycki and colleagues investigate the role of primary cilia in skeletal muscle satellite stem cells. They report on the specific association of primary cilia with quiescent and self-renewing satellite cells during adult myogenesis. Blocking cilia reassembly following cell division impairs satellite cell self-renewal, demonstrating that primary cilia are intrinsic cues required for stem cell self-renewal.

Satellite cells that reside on the myofibre surface are crucial for the muscle homeostasis and regeneration. Aging goes along with a less effective regeneration of skeletal muscle tissue mainly due to the decreased myogenic capability of satellite cells. This phenomenon impedes proper maintenance and contributes to the age-associated decline in muscle mass, known as sarcopenia. The myogenic potential impairment does not depend on a reduced myogenic cell number, but mainly on their difficulty to complete a differentiation program. The unbalanced production of reactive oxygen species in elderly people could be responsible for skeletal muscle impairments. microRNAs are conserved post-transcriptional regulators implicated in numerous biological processes including adult myogenesis. Here, we measure the ROS level and analyze myomiR (miR-1, miR-133b and miR-206) expression in human myogenic precursors obtained from Vastus lateralis of elderly and young subjects to provide the molecular signature responsible for the differentiation impairment of elderly activated satellite cells. publisher: Elsevier articletitle: Myomir dysregulation and reactive oxygen species in aged human satellite cells journaltitle: Biochemical and Biophysical Research Communications articlelink: http://dx.doi.org/10.1016/j.bbrc.2016.03.030 content_type: article copyright: Copyright © 2016 The Authors. Published by Elsevier Inc. ispartof: Biochemical and Biophysical Research Communications vol:473 issue:2 pages:462-70 ispartof: location:United States status: published

In this work we perform a high-resolution spectroscopic investigation of Eu3+-Ce3+ and Pr3+-Ce3+ codoped Y2SiO5 crystals. Satellite line spectra were recorded at low temperatures around the Eu3+:F-7(0) -> D-5(0) and the Pr3+:H-3(4) -> D-1(2) transitions. It is observed that the incorporation of Ce3+ as a codopant notably changes the Eu3+ and Pr3+ satellite line patterns. Satellite lines measured in singly doped Eu3+:Y2SiO5 were found at the same spectral positions in Eu3+-Ce3+ codoped crystals. These coincident lines were concluded to be due to pairs of Eu3+ ions. Extra satellite lines appeared in the codoped crystals, which were assigned to Ce3+ related structures such as Ce3+-Eu3+ pairs. The analysis of the Pr3+ satellite line spectra presents further challenges. Satellite lines associated to Pr3+ pairs show weaker intensity, presumably due to the efficient quenching of the Pr3+ D-1(2) emission through cross-relaxation paths (D-1(2) -> (1)G(4); H-3(4) -> F-3(4)). The investigation of the Eu3+ and Pr3+ satellite line patterns in Y2SiO5 is particularly interesting for their exploitation in rare-earth based quantum computation schemes. (C) 2015 Elsevier B.V. All rights reserved. (Less)

Host proteins are the integral part of a successful infection caused by a given RNA virus pathogenic to plants. Therefore, identification of crucial host proteins playing an important role in establishing the infection process is likely to help in devising approaches to curbing disease spread. Cucumber mosaic virus (Q-CMV) and its satellite RNA (QsatRNA) are important pathogens of many economically important crop plants worldwide. In a previous study, we demonstrated the biological significance of a Bromodomain containing RNA-binding Protein (BRP1) in the infection cycle of QsatRNA, making BRP1 an important host protein to study. To further shed a light on the mechanistic role of BRP1 in the replication of Q-CMV and QsatRNA, we analyzed the Nicotiana benthamiana host protein interactomes either for BRP1 alone or in the presence of Q-CMV or QsatRNA. Co-immunoprecipitation, followed by LC–MS/MS analysis of BRP1-FLAG on challenging with Q-CMV or QsatRNA has led us to observe a shift in the host protein interactome of BRP1. We discuss the significance of these results in relation to Q-CMV and its QsatRNA infection cycle. Biological significance Host proteins play an important role in replication and infection of eukaryotic cells by a wide-range of RNA viruses pathogenic to humans, animals and plants. Since a given eukaryotic cell typically contains ~ 30,000 different proteins, recent advances made in proteomics and bioinformatics approaches allowed the identification of host proteins critical for viral replication and pathogenesis. Although Cucumber mosaic virus (CMV) and its satRNA are well characterized at molecular level, information concerning the network of host factors involved in their replication and pathogenesis is still on its infancy. We have recently observed that a Bromodomain containing host protein (BRP1) is obligatory to transport satRNA to the nucleus. Consequently, it is imperative to apply proteomics and bioinformatics approaches in deciphering how host interactome network regulates the replication of CMV and its satRNA. In this study, first we established the importance of BRP1 in CMV replication. Then, application of co-immunoprecipitation in conjunction with LC–MS/MS allowed the identification of a wide range of host proteins that are associated with the replication of CMV and its satRNA. Interestingly, a shift in the plant proteome was observed when plants infected with CMV were challenged with its satRNA.

SummaryThe local synthesis of transmembrane proteins underlies functional specialization of dendritic microdomains in neuronal plasticity. It is unclear whether these proteins have access to the complete machinery of the secretory pathway following local synthesis. In this study, we describe a probe called pGolt that allows visualization of Golgi-related organelles for live imaging in neurons. We show that pGolt labels a widespread microsecretory Golgi satellite (GS) system that is, in contrast to Golgi outposts, present throughout basal and apical dendrites of all pyramidal neurons. The GS system contains glycosylation machinery and is localized between ERGIC and retromer. Synaptic activity restrains lateral movement of ERGIC, GS, and retromer close to one another, allowing confined processing of secretory cargo. Several synaptic transmembrane proteins pass through and recycle back to the GS system. Thus, the presence of an ER-ERGIC-GS-retromer microsecretory system in all neuronal dendrites enables autonomous local control of transmembrane protein synthesis and processing.

We are entering into an exciting era of genomics where truly complete, high-quality assemblies of human chromosomes are available end-to-end, or from 'telomere-to-telomere' (T2T). This technological advance offers a new opportunity to include endogenous human centromeric regions in high-resolution, sequence-based studies. These emerging reference maps are expected to reveal a new functional landscape in the human genome, where centromere proteins, transcriptional regulation, and spatial organization can be examined with base-level resolution across different stages of development and disease. Such studies will depend on innovative assembly methods of extremely long tandem repeats (ETRs), or satellite DNAs, paired with the development of new, orthogonal validation methods to ensure accuracy and completeness. This review reflects the progress in centromere genomics, credited by recent advancements in long-read sequencing and assembly methods. In doing so, I will discuss the challenges that remain and the promise for a new period of scientific discovery for satellite DNA biology and centromere function.

Identification of tumor-initiating populations could provide insights into tumor heterogeneity and responses to treatments, but this has proven difficult in most cancers. Now in Cell Stem Cell, Preussner et al. (2018) provide direct evidence that regenerating muscle satellite cells can be transformed to initiate and propagate rhabdomyosarcoma tumors.

Summary Identification of human satellite cells that fulfill muscle stem cell criteria is an unmet need in regenerative medicine. This hurdle limits understanding how closely muscle stem cell properties are conserved among mice and humans and hampers translational efforts in muscle regeneration. Here, we report that PAX7 satellite cells exist at a consistent frequency of 2–4 cells/mm of fiber in muscles of the human trunk, limbs, and head. Xenotransplantation into mice of 50–70 fiber-associated, or 1,000–5,000 FACS-enriched CD56+/CD29+ human satellite cells led to stable engraftment and formation of human-derived myofibers. Human cells with characteristic PAX7, CD56, and CD29 expression patterns populated the satellite cell niche beneath the basal lamina on the periphery of regenerated fibers. After additional injury, transplanted satellite cells robustly regenerated to form hundreds of human-derived fibers. Together, these findings conclusively delineate a source of bona-fide endogenous human muscle stem cells that will aid development of clinical applications., Highlights • CD56 and CD29 mark PAX7 satellite cells in diverse human muscles • Transplanted human satellite cells engraft, self-renew, and regenerate • Human adult muscle stem cells reside within the CD56+/CD29+ satellite cell pool, In this article Pomerantz and colleagues demonstrate that human skeletal muscle stem cells reside within the satellite cell pool at similar frequencies in diverse adult muscles and engraft, populate the stem cell niche, and regenerate after transplantation.

A liver bile acids transporter, sodium taurocholate cotransporting polypeptide (NTCP, encoded by SLC10A1) was recently identified as a functional receptor for hepatitis B virus (HBV) and its satellite hepatitis D virus (HDV). NTCP-complemented human hepatoma HepG2 cells (HepG2-NTCP) were shown to support infection of HBV and HDV in vitro, providing a much-needed and convenient cell culture system for the viruses. Identification of NTCP as a functional receptor for HBV has significantly advanced our understanding of the viral life cycle and opened new opportunities for developing anti-HBV interventions. This article forms part of a symposium in Antiviral Research on “An unfinished story: from the discovery of the Australia antigen to the development of new curative therapies for hepatitis B”.

The 356 nt noncoding satellite RNA C (satC) of Turnip crinkle virus (TCV) is composed of 5′ sequences from a second TCV satRNA (satD) and 3′ sequences derived from TCV. SHAPE structure mapping revealed that 76 nt in the poorly-characterized satD-derived region form an extended hairpin (H2). Pools of satC in which H2 was replaced with 76, 38, or 19 random nt were co-inoculated with TCV helper virus onto plants and satC fitness assessed using in vivo functional selection (SELEX). The most functional progeny satCs, including one as fit as wild-type, contained a 38–39 nt H2 region that adopted a hairpin structure and exhibited an increased ratio of dimeric to monomeric molecules. Some progeny of satC with H2 deleted featured a duplication of 38 nt, partially rebuilding the deletion. Therefore, H2 can be replaced by a 38–39 nt hairpin, sufficient for overall structural stability of the 5′ end of satC.

A chiral-aptasensor for ochratoxin A (OTA) detection based on Au core–Ag nanoparticle satellite assemblies was fabricated for the first time. High yields of Au core–Ag NP satellite assemblies were prepared in the aqueous phase and the optical properties of the Au core–Ag NP satellite assemblies were investigated in detail. Because of the different concentrations of the OTA target, the assembly degree of the architecture varied which led to the corresponding chiral signals. The developed method for OTA detection with excellent linear range from 1 to 50 pg/mL showed high selectivity for OTA and the limit of detection as low as 0.16 pg/mL. The feasibility of this method was demonstrated by performing recovery experiment using negative red wine samples, excellent recovery ranged from 90% to 105% was achieved, and indicated promising applications.

Intratumoral therapy with bacteria/bacterial products dates to at least the 1890s. Over the decades this has expanded beyond the use of microbes and microbial products to include chemicals, cancer chemotherapeutic agents, cytokines, recombinant organisms, and hybrid molecules. The appeal of this method of delivery is the ability to deliver high concentrations of the therapeutic agent directly to the tumor, often with minimal side effects. This article summarizes the use and efficacy of the various agents used in the past and present in the treatment of in-transit and satellite metastases in melanoma.

Duchenne muscular dystrophy is an inherited disorder that is characterized by progressive skeletal muscle weakness and wasting, with a failure of muscle maintenance/repair mediated by satellite cells (muscle stem cells). The function of skeletal muscle stem cells resident in dystrophic muscle may be perturbed by being in an increasing pathogenic environment, coupled with constant demands for repairing muscle. To investigate the contribution of satellite cell exhaustion to this process, we tested the functionality of satellite cells isolated from the mdx mouse model of Duchenne muscular dystrophy. We found that satellite cells derived from young mdx mice contributed efficiently to muscle regeneration within our in vivo mouse model. To then test the effects of long-term residence in a dystrophic environment, satellite cells were isolated from aged mdx muscle. Surprisingly, they were as functional as those derived from young or aged wild type donors. Removing satellite cells from a dystrophic milieu reveals that their regenerative capacity remains both intact and similar to satellite cells derived from healthy muscle, indicating that the host environment is critical for controlling satellite cell function., Highlights • Grafted mdx satellite cells regenerate muscle as well as wild-type satellite cells. • Aged mdx myofibers bear more satellite cells than aged wild type fibers. • mdx satellite cells retain their ability to activate. • Aged mdx satellite cells are robustly regenerative in vivo.

How resident stem cells and their immediate progenitors rebuild tissues of pre-injury organization and size for proportional regeneration is not well understood. Using 3D, time-lapse intravital imaging for direct visualization of the muscle regeneration process in live mice, we report that extra-cellular matrix remnants from injured skeletal muscle fibers, “ghost fibers,” govern muscle stem/progenitor cell behaviors during proportional regeneration. Stem cells were immobile and quiescent without injury whereas their activated progenitors migrated and divided after injury. Unexpectedly, divisions and migration were primarily bi-directionally oriented along the ghost fiber longitudinal axis, allowing for spreading of progenitors throughout ghost fibers. Re-orienting ghost fibers impacted myogenic progenitors’ migratory paths and division planes, causing disorganization of regenerated muscle fibers. We conclude that ghost fibers are autonomous, architectural units necessary for proportional regeneration after tissue injury. This finding reinforces the need to fabricate bioengineered matrices that mimic living tissue matrices for tissue regeneration therapy.

Satellite cells comprise a pool of quiescent stem cells that repair muscle damage, but the mechanisms enforcing their quiescence are poorly defined. In this issue of Cell Stem Cell, Boonsanay et al. (2016) show that the histone methyltransferase Suv4-20H1 maintains satellite cell quiescence by promoting a heterochromatic state through transcriptional repression of the myogenic master regulator MyoD.