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Background: Irradiation disrupts the vascular niche where hematopoietic stem cells (HSCs) reside, causing delayed hematopoietic reconstruction. The subsequent recovery of sinusoidal vessels is key to vascular niche regeneration and a prerequisite for hematopoietic reconstruction. We hypothesize that resident bone marrow macrophages (BM-Mφs) are responsible for repairing the HSC niche upon irradiation injury. Methods: We examined the survival and activation of BM-Mφs in C57BL/6 mice upon total body irradiation. After BM-Mφ depletion via injected clodronate-containing liposomes and irradiation injury, hematopoietic reconstruction and sinusoidal vascular regeneration were assessed with immunofluorescence and flow cytometry. Then enzyme-linked immunosorbent assay (ELISA) and flow cytometry were performed to analyze the contribution of VEGF-A released by BM-Mφs to the vascular restructuring of the HSC niche. VEGF-A-mediated signal transduction was assessed with transcriptome sequencing, flow cytometry, and pharmacology (agonists and antagonists) to determine the molecular mechanisms of Piezo1-mediated responses to structural changes in the HSC niche. Results: The depletion of BM-Mφs aggravated the post-irradiation injury, delaying the recovery of sinusoidal endothelial cells and HSCs. A fraction of the BM-Mφ population persisted after irradiation, with residual BM-Mφ exhibiting an activated M2-like phenotype. The expression of VEGF-A, which is essential for sinusoidal regeneration, was upregulated in BM-Mφs post-irradiation, especially CD206+ BM-Mφs. The expression of mechanosensory ion channel Piezo1, a response to mechanical environmental changes induced by bone marrow ablation, was upregulated in BM-Mφs, especially CD206+ BM-Mφs. Piezo1 upregulation was mediated by the effects of irradiation, the activation of Piezo1 itself, and the M2-like polarization induced by the phagocytosis of apoptotic cells. Piezo1 activation was associated with increased expression of VEGF-A and increased accumulation of NFATC1, NFATC2, and HIF-1α. The Piezo1-mediated upregulation in VEGF-A was suppressed by inhibiting the calcineurin/NFAT/HIF-1α signaling pathway. Conclusion: These findings reveal that BM-Mφs play a critical role in promoting vascular niche regeneration by sensing and responding to structural changes after irradiation injury, offering a potential target for therapeutic efforts to enhance hematopoietic reconstruction.

Megakaryocytes (MKs) are the unique non-pathological cells that undergo polyploidization in mammals. The polyploid formation is critical for understanding the MK biology, and transcriptional regulation is involved in the differentiation and maturation of MKs. However, little is known about the functions of transcriptional elongation factors in the MK polyploidization. In this study, we investigated the role of transcription elongation factor EloA in the polyploidy formation during the MK differentiation. We found that EloA was highly expressed in the erythroleukemia cell lines HEL and K562. Knockdown of EloA in HEL cell line was shown to impair the phorbol myristate acetate (PMA) induced polyploidization process, which was used extensively to model megakaryocytic differentiation. Selective over-expression of EloA mutants with Pol II elongation activity partially restored the polyploidization. RNA-sequencing revealed that knockdown of EloA decelerated the transcription of genes enriched in the ERK1/2 cascade pathway. The phosphorylation activity of ERK1/2 decreased upon the EloA inhibition, and the polyploidization process of HEL was hindered when ERK1/2 phosphorylation was inhibited by PD0325901 or SCH772984. This study evidenced a positive role of EloA in HEL polyploidization upon PMA stimulation through enhanced ERK1/2 activity. [ABSTRACT FROM AUTHOR]

The complete mitochondrial genome of the stone loach Triplophysa stoliczkae is 16,571 bp in size, consisting of 13 protein-coding genes, 22 transfer RNA (tRNA) genes, two ribosomal RNA (rRNA) genes, and a noncoding control region. As in other vertebrates, most mitochondrial genes are encoded on the heavy strand, except for nd6 and eight tRNA genes which are encoded on the light strand. The overall base composition of the heavy strand of the T. stoliczkae mitochondrial genome is A: 28.1%, T: 29.0%, C: 25.0%, and G: 17.9%. The alignment of the Triplophysa species control regions exhibited high genetic variability and rich A+T content. [ABSTRACT FROM AUTHOR]

The complete mitochondrial genome of the stone loachTriplophysa bleekericollected from the Anning River, a tributary of the Yalong River, in Sichuan Province was sequenced. The genome is 16,573 bp in length, consisting of 13 protein-coding genes, 22 transfer RNA (tRNA) genes, two ribosomal RNA (rRNA) genes, and a noncoding control region. Most of the genes are encoded on the heavy strand, except forND6and eight tRNAs. The overall base composition ofT. bleekeriis 28.1% for A, 28.4% for T, 25.5% for C, 18.0% for G, with a slight A+T bias of 56.5%. The complete mitochondrial genetic variability is high among differentTriplophysaspecies and between the twoT. bleekeriindividuals from different rivers. [ABSTRACT FROM AUTHOR]

The complete mitochondrial genome of theTriplophysa robustahas been determined in this study. It is 16,572 bp in size and consists of 13 protein-coding genes, 22 tRNA genes, two rRNA genes, and one non-coding control region (D-loop). The overall base composition of the heavy strand of theT. robustamitochondrial genome was A: 28.20%, T: 28.27%, C: 25.37%, and G: 18.16%. The total length of the 13 protein-coding genes was 11,428 bp. Analysis of the genes indicated the high genetic variability amongTriplophysaspecies. [ABSTRACT FROM PUBLISHER]

The complete mitochondrial DNA genome ofPtychobarbus kaznakoviwas sequenced and characterized. The genome is 16,842 bp in length. Similar with most teleosts, it has two ribosomal RNA (rRNA) genes, 13 protein-coding genes, 22 transfer RNA (tRNA) genes, and one displacement loop (D-loop) region. Conserved sequence blocks, including ETAS, CSB-B, D, E, F, and CSB1-3, were identified in the D-loop, which is similar to other species in Cypriniformes. Nevertheless, a 55 bp tandem repeat array was also identified at 3′ end of the D-loop, which is the first finding in Schizothoracinae. Phylogenetic analysis showed that the species ofPtychobarbus(P. dipogonandP. kaznakovi) formed a monophyletic group and represented close relationship to the species without scales in Schizothoracinae. [ABSTRACT FROM PUBLISHER]