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Background: Fibroblast Growth Factor 20 (FGF20)‐FGF receptor 1 (FGFR1) signaling is essential for cochlear hair cell (HC) and supporting cell (SC) differentiation. In other organ systems, FGFR1 signals through several intracellular pathways including MAPK (ERK), PI3K, phospholipase C ɣ (PLCɣ), and p38. Previous studies implicated MAPK and PI3K pathways in HC and SC development. We hypothesized that one or both would be important downstream mediators of FGF20‐FGFR1 signaling for HC differentiation. Results: By inhibiting pathways downstream of FGFR1 in cochlea explant cultures, we established that both MAPK and PI3K pathways are required for HC differentiation while PLCɣ and p38 pathways are not. Examining the canonical PI3K pathway, we found that while AKT is necessary for HC differentiation, it is not sufficient to rescue the Fgf20−/− phenotype. To determine whether PI3K functions downstream of FGF20, we inhibited Phosphatase and Tensin Homolog (PTEN) in Fgf20−/− explants. Overactivation of PI3K resulted in a partial rescue of the Fgf20−/− phenotype, demonstrating a requirement for PI3K downstream of FGF20. Consistent with a requirement for the MAPK pathway for FGF20‐regulated HC differentiation, we show that treating Fgf20−/− explants with FGF9 increased levels of dpERK. Conclusions: Together, these data provide evidence that both MAPK and PI3K are important downstream mediators of FGF20‐FGFR1 signaling during HC and SC differentiation. Key Findings: PI3K and MEK1/2 are necessary for hair cell differentiation while p38 and PLCγ are not.pAKT is necessary but not sufficient for hair cell differentiation.PTEN inhibition partially rescues Fgf20 knockout phenotype.dpERK is downstream of FGF20‐FGFR1 signaling. [ABSTRACT FROM AUTHOR]

SUMMARY: Species are becoming extinct at unprecedented rates as a consequence of human activity. Hence it is important to understand the evolutionary dynamics of species with already small population sizes. Populus ilicifolia is a vulnerable poplar species that is isolated from other poplar species and is uniquely adapted to the Tropics. It has a very limited size, reproduces partly clonally and is therefore an excellent case study for conservation genomics. We present here the first annotated draft genome of P. ilicifolia, characterize genome‐wide patterns of polymorphisms and compare those to other poplar species with larger natural ranges. P. ilicifolia experienced a more prolonged and severe decline of effective population size (Ne) and signs of genetic erosion than any other poplar species with which it was compared. At present, the species has the lowest genome‐wide genetic diversity, the highest abundance of long runs of homozygosity, high inbreeding levels as well as a high overall accumulation of deleterious variants. However, more effective purging of severely deleterious variants and adaptation to the Tropics may have contributed to its survival. Hence, in spite of its limited genetic variation, it is certainly worth pursuing the conservation efforts of this unique species. Significance Statement: Whole‐genome sequencing of Populus ilicifolia, a vulnerable and isolated poplar tree from the Tropics that can reproduce both sexually and asexually, was used to explore how population history and reproduction affected its genetic characteristics, genetic load, and its potential for tropical adaptation. [ABSTRACT FROM AUTHOR]

We characterized the chloroplast (cp) genome sequence of Banara guianensis by using Illumina pair-end sequencing platform, and the complete whole cp genome was 158,577 bp. That contains a large single copy region (LSC) of 85,863 bp and a small single copy region (SSC) of 17,334 bp, which were separated by a pair of 27,690 bp inverted repeat regions (IRs). The cp genome has 112 annotated genes, including 76 protein-coding genes and 36 tRNA genes. The overall GC content of it is 36.5%, while the corresponding values of the LSC, SSC and IR regions are 34.3, 30.2 and 42.0%, respectively. Furthermore, the phylogenetic analysis suggested that the location of B. guianensis is a sister of A. serrata and is an outgroup of other Salicaceae species. [ABSTRACT FROM AUTHOR]

Summary Cell fate transitions are essential for specification of stem cells and their niches, but the precise timing and sequence of molecular events during embryonic development are largely unknown. Here, we identify, with 3D and 4D microscopy, unclustered precursors of dermal condensates (DC), signaling niches for epithelial progenitors in hair placodes. With population-based and single-cell transcriptomics, we define a molecular time-lapse from pre-DC fate specification through DC niche formation and establish the developmental trajectory as the DC lineage emerges from fibroblasts. Co-expression of downregulated fibroblast and upregulated DC genes in niche precursors reveals a transitory molecular state following a proliferation shutdown. Waves of transcription factor and signaling molecule expression then coincide with DC formation. Finally, ablation of epidermal Wnt signaling and placode-derived FGF20 demonstrates their requirement for pre-DC specification. These findings uncover a progenitor-dependent niche precursor fate and the transitory molecular events controlling niche formation and function. Graphical Abstract Highlights • Precursors of the hair follicle niche are specified before niche cluster formation • Bulk and single-cell transcriptomics defines niche fate at molecular transitional state • Successive transcription factor and signaling waves mark niche fate acquisition • Niche fate acquisition is not "pre-programmed" and requires FGF20 from progenitors Mok et al. identify niche precursors during progenitor and niche formation in mouse embryonic hair follicles. Population-based and single-cell transcriptomics show that unclustered dermal condensate precursors are at a transitional fibroblast-to-DC state marked by successive waves of transcription factor and signaling molecule expression. Niche fate acquisition is not "pre-programmed" and requires placode progenitor-derived FGF20. [ABSTRACT FROM AUTHOR]

Introduction: Moyamoya disease (MMD) is a chronic cerebrovascular disease that can lead to ischemia and hemorrhagic stroke. The relationship between oxidative phosphorylation (OXPHOS) and MMD pathogenesis remains unknown. Methods: The gene expression data of 60 participants were acquired from three Gene Expression Omnibus (GEO) datasets, including 36 and 24 in the MMD and control groups. Differentially expressed genes (DEGs) between MMD patients MMD and control groups were identified. Machine learning was used to select the key OXPHOS-related genes associated with MMD from the intersection of DEGs and OXPHOS-related gene sets. Gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), gene set enrichment analysis (GSEA), Immune infiltration and microenvironments analysis were used to analyze the function of key genes. Machine learning selected four key OXPHOS-related genes associated with MMD: CSK , NARS2 , PTPN6 and SMAD2 ( PTPN6 was upregulated and the other three were downregulated). Results: Functional enrichment analysis showed that these genes were mainly enriched in the Notch signaling pathway, GAP junction, and RNA degradation, which are related to several biological processes, including angiogenesis, proliferation of vascular smooth muscle and endothelial cells, and cytoskeleton regulation. Immune analysis revealed immune infiltration and microenvironment in these MMD samples and their relationships with four key OXPHOS-related genes. APC co-inhibition ( p = 0.032), HLA ( p = 0.001), MHC I ( p = 0.013), T cellco- inhibition ( p = 0.032) and Type I IFN responses ( p < 0.001) were significantly higher in the MMD groups than those in the control groups. The CSK positively correlated with APC co-inhibition and T cell-co-inhibition. The NARS2 negatively correlated with Type I IFN response. The SMAD2 negatively correlated with APC co-inhibition and Type I IFN response. The PTPN6 positively correlated with HLA, MHC I and Type I IFN responses. Discussion: This study provides a comprehensive understanding of the role of OXPHOS in MMD and will contribute to the development of new treatment methods and exploration of MMD pathogenesis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Han, Zhang, Su, Zhou, Wang, Xu, Zhao, He and Wang.)