TGF-β signaling plays an essential role in the lineage specification of mesenchymal stem/progenitor cells in fetal bone marrow
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ABSTRACT:
PROVIDER: PRJNA542928 | ENA |
REPOSITORIES: ENA
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Project description:TGF-β regulates fetale bone marrow niche emergence. Abrogating TGF-β signaling in mesenchymal cells during development results in a marked expansion of adipocytes and CAR cells in the bone marrow, while osteoblasts are reduced. RNA expression data from Osx-Cre targeted mesenchymal stromal cells obtained from E16.5 mouse hindlimbs of transgenic mice lacking Tgfbr2 in mesenchymal stromal cells or littermate controls.
2019-05-15 | GSE131219 | GEO
Project description:Mesenchymal stromal cells are key components of hematopoietic niches in the bone marrow. Here we abrogated transforming growth factor β (TGF-β) signaling in mesenchymal stem/progenitor cells (MSPCs) by deleting Tgfbr2 in mesenchymal cells using a doxycycline-repressible Sp7 (osterix)-Cre transgene. We show that loss of TGF-β signaling during fetal development results in a marked expansion of CXCL12-abundant reticular (CAR) cells and adipocytes in the bone marrow, while osteoblasts are significantly reduced. These stromal alterations are associated with significant defects in hematopoiesis, including a shift from lymphopoiesis to myelopoiesis. However, hematopoietic stem cell function is preserved. Interestingly, TGF-β signaling is dispensable for the maintenance of mesenchymal cells in the bone marrow after birth under steady-state conditions. Collectively, these data show that TGF-β plays an essential role in the lineage specification of fetal but not definitive MSPCs and is required for the establishment of normal hematopoietic niches in fetal and perinatal bone marrow.
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Project description:Dendritic cells (DCs) in lymphoid tissue comprise conventional DCs (cDCs) and plasmacytoid DCs (pDCs) that develop from common DC progenitors (CDPs). CDPs are Flt3+c-kitintM-CSFR+ and reside in bone marrow. Here we describe a two-step culture system that recapitulates DC development from c-kithiFlt3-/lo multipotent progenitors (MPPs) into CDPs and further into cDC and pDC subsets. MPPs and CDPs are amplified in vitro with Flt3 ligand, stem cell factor, hyper-IL-6 and insulin- like growth factor-1. The four-factor cocktail readily induces self-renewal of MPPs and their progression into CDPs and has no self-renewal activity on CDPs. The amplified CDPs respond to all known DC poietins and generate all lymphoid tissue DCs in vivo and in vitro. Additionally, in vitro CDPs recapitulate the cell surface marker and gene expression profile of in vivo CDPs and possess a DC-primed transcription profile. Transforming growth factor-β1 (TGF-β1) impacts on CDPs and directs their differentiation towards cDCs. Genome-wide gene expression profiling of TGF-β1-induced genes identified transcription factors, such as interferon regulatory factor-4 (IRF-4) and RelB, that are implicated as instructive factors for cDC subset specification. TGF-β1 also induced the transcription factor inhibitor of differentiation/DNA binding 2 (Id2) that suppresses pDC development. Thus, TGF-β1 directs CDP differentiation into cDC by inducing both cDC instructive factors and pDC inhibitory factors. 20 samples in total. Multipotent progenitor - MPP_1 - MPP_2 Common dendritic cell progenitor - CDP_1 - CDP_2 Plasmacytoid dendritic cell - pDC_1 - pDC_2 Conventional dendritic cell - cDC_1 - cDC_2 In vivo common dendritic cell progenitor - In vivo CDP_1 - In vivo CDP_2 Untreated common dendritic cell progenitor (CDP) - CDP_0h_1 - CDP_0h_2 TGF-beta1 treated (4 hours) CDP - CDP_4h_1 - CDP_4h_2 TGF-beta1 treated (8 hours) CDP - CDP_8h_1 - CDP_8h_2 TGF-beta1 treated (12 hours) CDP - CDP_12h_1 - CDP_12h_2 TGF-beta1 treated (24 hours) CDP - CDP_24h_1 - CDP_24h_2
2010-10-04 | E-GEOD-22432 | biostudies-arrayexpress
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2024-04-02 | PXD042251 | Pride
Project description:Sex determination of the gonads begins with fate specification of gonadal supporting cells into either ovarian granulosa cells or testicular Sertoli cells. This process of fate specification hinges on a balance of transcriptional control. We discovered that the transcription factor RUNX1 is enriched in the fetal ovary in rainbow trout, turtle, mouse, and human. In the mouse, RUNX1 marks the supporting cell lineage and becomes granulosa cell-specific as the gonads differentiate. RUNX1 plays complementary/redundant roles with FOXL2 to maintain fetal granulosa cell identity, and combined loss of RUNX1 and FOXL2 results in masculinization of the fetal ovaries. To determine whether interplay between RUNX1 and FOXL2 occurs at the chromatin level, we performed genome-wide analysis of RUNX1 chromatin occupancy in E14.5 ovaries. The top de novo motif identified in RUNX1 ChIP-seq matched the RUNX motif. We found that RUNX1 chromatin occupancy was partially overlapping with FOXL2 chromatin occupancy in fetal ovaries.
2019-04-02 | GSE128767 | GEO
Project description:Recent studies demonstrate that Ca2+ signaling has an important role in EMT. Use of Ca2+ blockers such as 2APB can inhibit cell migration induced by TGF-β. Interestingly, we see an unexpected increase in Snail expression upon Ca2+ blocker treatment of both MCF10A and NMuMG cells; this increase is not observed with 2APB treatment alone. Therefore, we believe that 2APB plays a synergistic role with TGF-β in Snail induction. We propose to investigate the gene networks that change following 2APB +TGF-β treatment.
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Project description:Recent advances in pancreatic differentiation from human pluripotent stem cells (hPSCs) hold great potentials for disease modeling and regenerative medicine, and more precise control over the dynamic differentiation process is critical. N6-methyladenosine (m6A) is the most prevalent internal messenger RNA (mRNA) modification, while the roles of m6A mark in pancreatic differentiation and development remain elusive. In addition, ALKBH5 is a major mRNA m6A demethylase and its role in pancreatic differentiation has not been reported. Here, we firstly studied mRNA m6A dynamics during pancreatic differentiation from hPSCs. Next, using the CRISPR-based genome editing tool, we generated ALKBH5 knockout hPSC lines and found that ALKBH5 plays important roles in pancreatic specification. After that, we conducted a series of functional and mechanistic studies, and demonstrated that ALKBH5 modulated many important genes involved in pancreatic differentiation. Collectively, our findings identified ALKBH5 as an essential regulator of human pancreatic differentiation and highlighted that m6A modification presents a new layer of regulation at epitranscriptome levels during cell-fate specification.
2022-06-13 | GSE163963 | GEO
Project description:Recent advances in pancreatic differentiation from human pluripotent stem cells (hPSCs) hold great potentials for disease modeling and regenerative medicine, and more precise control over the dynamic differentiation process is critical. N6-methyladenosine (m6A) is the most prevalent internal messenger RNA (mRNA) modification, while the roles of m6A mark in pancreatic differentiation and development remain elusive. In addition, ALKBH5 is a major mRNA m6A demethylase and its role in pancreatic differentiation has not been reported. Here, we firstly studied mRNA m6A dynamics during pancreatic differentiation from hPSCs. Next, using the CRISPR-based genome editing tool, we generated ALKBH5 knockout hPSC lines and found that ALKBH5 plays important roles in pancreatic specification. After that, we conducted a series of functional and mechanistic studies, and demonstrated that ALKBH5 modulated many important genes involved in pancreatic differentiation. Collectively, our findings identified ALKBH5 as an essential regulator of human pancreatic differentiation and highlighted that m6A modification presents a new layer of regulation at epitranscriptome levels during cell-fate specification.
2022-06-13 | GSE163945 | GEO