Pinch loss in early mesenchymal progenitors alters bone marrow environment
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA638652 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11990513.fastq.gz | Fastqsanger.gz | |||
| SRR11990514.fastq.gz | Fastqsanger.gz | |||
| SRR11990515.fastq.gz | Fastqsanger.gz | |||
| SRR11990516.fastq.gz | Fastqsanger.gz | |||
| SRR11990517.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 6 |
Similar Datasets
Project description:To investigate the alteration of bone marrow environment caused by Pinch loss, we performed single-cell RNA-sequencing on bone marrow cells, including hematopoietic cells and non-hematopietic stromal cells. As results indicated, we found both cell type proportion and transcriptomic signatures were dramatically altered by Pinch loss. We identified genes related to ossification, extracellular matrix organization, skeletal system development, and vasculature structure development were significantly differentially expressed between control group and dKO group in many mesenchymal stromal cells. Our results revealed Pinch loss disrupted homeostasis of bone marrow niche, monocytes in bone marrow were actively involved in inflammatory response, and functions of mesenchymal stromal cells was severely disrupted.
2023-12-08 | GSE152217 | GEO
Project description:Adaptation to low oxygen tension (hypoxia) is a critical event during development. The transcription factors Hypoxia Inducible Factor-1α (HIF-1α) and HIF-2α are essential mediators of the homeostatic responses that allow hypoxic cells to survive and differentiate. Von Hippel-Lindau protein (VHL) is the E3 ubiquitin ligase that targets HIFs to the proteasome for degradation in normoxia. We have previously demonstrated that the transcription factor HIF-1α is essential for survival and differentiation of growth plate chondrocytes, whereas HIF-2α is not necessary for fetal growth plate development. We have also shown that VHL is important for endochondral bone development, since loss of VHL in chondrocytes causes severe dwarfism. In this study, in order to expand our understanding of the role of VHL in chondrogenesis, we conditionally deleted VHL in mesenchymal progenitors of the limb bud, i.e. in cells not yet committed to the chondrocyte lineage. Deficiency of VHL in limb bud mesenchyme does not alter the timely differentiation of mesenchymal cells into chondrocytes. However, it causes structural collapse of the cartilaginous growth plate as a result of impaired proliferation, delayed terminal differentiation, and ectopic death of chondrocytes. This phenotype is associated to delayed replacement of cartilage by bone. Notably, loss of HIF-2α fully rescues the late formation of the bone marrow cavity in VHL mutant mice, though it does not affect any other detectable abnormality of the VHL mutant growth plates. Our findings demonstrate that VHL regulates bone morphogenesis as its loss considerably alters size, shape and overall development of the skeletal elements.
| S-EPMC4335807 | biostudies-literature
Project description:Postnatal bone marrow houses mesenchymal progenitor cells that are osteoblast precursors. These cells have established therapeutic potential, but they are difficult to maintain and expand in vitro, presumably because little is known about the mechanisms controlling their fate decisions. To investigate the potential role of Notch signaling in osteoblastogenesis, we used conditional alleles to genetically remove components of the Notch signaling system during skeletal development. We found that disruption of Notch signaling in the limb skeletogenic mesenchyme markedly increased trabecular bone mass in adolescent mice. Notably, mesenchymal progenitors were undetectable in the bone marrow of mice with high bone mass. As a result, these mice developed severe osteopenia as they aged. Moreover, Notch signaling seemed to inhibit osteoblast differentiation through Hes or Hey proteins, which diminished Runx2 transcriptional activity via physical interaction. These results support a model wherein Notch signaling in bone marrow normally acts to maintain a pool of mesenchymal progenitors by suppressing osteoblast differentiation. Thus, mesenchymal progenitors may be expanded in vitro by activating the Notch pathway, whereas bone formation in vivo may be enhanced by transiently suppressing this pathway.
| S-EPMC2740725 | biostudies-literature
Project description:We describe the proteomic composition of the extracellular environment of fetal and adult hematopoietic progenitors by data-independent acquisition mass spectrometry analysis.
2024-04-02 | PXD042251 | Pride
Project description:Microarray analysis of differentially expressed genes in wild-type and NFAT5-deficient hematopoietic stem cells (HSC) and multipotent progenitors (MPP)
2024-09-13 | GSE228575 | GEO
Project description:Stem cells have been demonstrated in the inner ear but they do not spontaneously divide to replace damaged sensory cells. Mesenchymal stem cells (MSC) from bone marrow have been reported to differentiate into multiple lineages including neurons, and we therefore asked whether MSCs could generate sensory cells. Overexpression of the prosensory transcription factor, Math1, in sensory epithelial precursor cells induced expression of myosin VIIa, espin, Brn3c, p27Kip, and jagged2, indicating differentiation to inner ear sensory cells. Some of the cells displayed F-actin positive protrusions in the morphology characteristic of hair cell stereociliary bundles. Hair cell markers were also induced by culture of mouse MSC-derived cells in contact with embryonic chick inner ear cells, and this induction was not due to a cell fusion event, because the chick hair cells could be identified with a chick-specific antibody and chick and mouse antigens were never found in the same cell.
| S-EPMC3136105 | biostudies-literature
Project description:Purpose: To compare the difference in gene expression between human limbal niche cells (LNC) and bone marrow derived mesenchymal stem cells (BMMSC). Methods: LNC were isolated by collagenase and expanded in modified embryonic stem cell medium (MESCM) on a Matrigel coated plastic plate. Cell diameters were measured with Image J software. Relative gene expression levels between LNC and BMMSC were compared using Affymetrix Human Primer View Gene Expression Array. A subset of differentially expressed genes was verified by RT-qPCR. The protein level of LAMA1 and COL4A1 was confirmed by Western blot and immunostaining. Results: The average diameter of LNC was 10.2±2.4 μm, which was significantly smaller than that of BMMSC (14 ±3.4 μm) (p<0.0001). Expression of 20,432 genes was examined by Gene Expression Array, among which expression of 349 genes in LNC was 10-fold or higher than that of BMMSC and expression of 8 genes in LNC was 100-fold or higher than that of BMMSC, while expression of 3 genes in BMMSC was 100-fold higher than that of LNC. GO analysis and pathway analysis showed that the differentially expressed genes were mainly enriched in the extracellular matrix receptor interaction pathway and Wnt signaling pathway. In addition, RT-qPCR results demonstrated that the expression of CD73, CD90, CD105, PDGFRβ, Vimentin, SCF, KIT (CD117), COL14A1, LAMA2, THBS2, FZD1, BMP2 and CXCL12 genes in LNC were at least 2 folds higher than BMMSC. The protein level of LAMA1 was higher but the protein level of COL4A1 was lower in LNC than that in BMMSC. Conclusion: LNC exhibit differential gene expression from BMMSC in the extracellular matrix (ECM) receptor interaction pathway and Wnt signaling pathway, suggesting that LNC have their unique signaling pathways to support limbal stem cell niches.
| S-EPMC7053302 | biostudies-literature
Project description:The cellular mechanisms required to ensure homeostasis of the hematopoietic niche and the ability of this niche to support hematopoiesis upon stress remain elusive. We here identify Wnt5a in Osterix+ mesenchymal progenitor and stem cells (MSPCs) as a critical factor for niche-dependent hematopoiesis. Mice lacking Wnt5a in MSPCs suffer from stress-related bone marrow (BM) failure and increased mortality. Niche cells devoid of Wnt5a show defective actin stress fiber orientation due to an elevated activity of the small GTPase CDC42. This results in incorrect positioning of autophagosomes and lysosomes, thus reducing autophagy and increasing oxidative stress. In MSPCs from patients from BM failure states which share features of peripheral cytopenia and hypocellular BM, we find similar defects in actin stress fiber orientation, reduced and incorrect colocalization of autophagosomes and lysosomes, and CDC42 activation. Strikingly, a short pharmacological intervention to attenuate elevated CDC42 activation in vivo in mice prevents defective actin-anchored autophagy in MSPCs, salvages hematopoiesis and protects against lethal cytopenia upon stress. In summary, our study identifies Wnt5a as a restriction factor for niche homeostasis by affecting CDC42-regulated actin stress-fiber orientation and autophagy upon stress. Our data further imply a critical role for autophagy in MSPCs for adequate support of hematopoiesis by the niche upon stress and in human diseases characterized by peripheral cytopenias and hypocellular BM.
| S-EPMC8814682 | biostudies-literature
Project description:De novo ASXL1 mutations are found in patients with Bohring-Opitz syndrome, a disease with severe developmental defects and early childhood fatality. The underlying pathologic mechanisms remain largely unknown. Using Asxl1-targeted murine models,we found that Asxl1 global loss or conditional deletion in osteoblasts and their progenitors in mice leads to significant bone loss and markedly decreased numbers of marrow mesenchymal stem/progenitor cells (MSPCs) compared with wild-type (WT) littermates. Asxl1-/- MSPCs displayed impaired self-renewal and skewed differentiation-away from osteoblasts and favoring adipocytes. RNA-seq analysis reveals the altered expression of genes involved in cell proliferation, skeletal development and morphogenesis. Furthermore, gene set enrichment analysis showed a decreased gene expression of stem cell self-renewal signature,suggesting the role of Asxl1 in regulating the stemness of MSPCs. Importantly, introducing Asxl1 normalized NANOG and OCT4 expression and restored the self-renewal capacity of Asxl1-/- MSPCs. Our study unveils a pivotal role of ASXL1 in maintenance of MSPC functions and skeletal development. Examination of mRNA profiles in wild type and Asxl1-/- MSPCs by deep sequencing
2016-06-30 | E-GEOD-75787 | biostudies-arrayexpress
Project description:RNA-seq analysis of differentially expressed genes in wild-type, NFAT5-deficient, IFNAR1-deficient and double deficient (NFAT5 and IFNAR1) hematopoietic stem cells (HSC) and multipotent progenitors (MPP)
2024-09-11 | GSE228634 | GEO