Mesoderm-derived PDGFRA+ cells regulate emergence of hematopoietic stem cells in the dorsal aorta
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PROVIDER: PRJNA471497 | ENA |
REPOSITORIES: ENA
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Project description:Mouse hematopoietic stem cells (HSCs) first emerge at embryonic day 10.5 (E10.5) on the ventral surface of the dorsal aorta, by endothelial-to-hematopoietic transition (EHT). We investigated whether cells with mesenchymal stem cell-like cell (MSC-LCs) activity that provide an essential niche for HSCs in the bone marrow reside in the aorta-gonad-mesonephros (AGM) and contribute to the structural development of the dorsal aorta and EHT. Using transgenic mice, we demonstrate a lineage hierarchy for AGM MSC-LCs and trace the aortic endothelium and HSCs to mesoderm-derived (Mesp1) PDGFRA+ cells. Mesp1/PDGFRA+ MSC-LCs dominate the sub-endothelial and ventral stroma in the E10.5–E11.5 AGM but by E13.5 are replaced by neural crest (Wnt1) MSC-LCs. Co-aggregating endothelial cells with Mesp1 but not with Wnt1 MSC-LCs resulted in EHT and generation of LT-HSCs that is interrupted by dose-dependent inhibition of PDGFRA signalling. This partnership between endothelial cells and AGM Mesp1 MSC-LCs could be harnessed to manufacture HSCs from endothelium.
2022-04-26 | GSE163757 | GEO
Project description:During embryonic development, the first hematopoietic stem cells (HSCs) arise from a transient population of endothelial cells lining the ventral surface of the dorsal aorta, via a process of endothelial to hematopoietic transition (EHT) at embryonic day (E) 10.5. This region contains resident PDGFRA+ stromal cells (PSCs), but their identity and role in HSC generation in the AGM are not well understood. Using a library of compound transgenic mice, we identified a population of PDGFRA+/Nestin-GFP (N-GFP)-/PDGFRB-/CD31- cells with PSC activity in the E10.5 and E11.5 mouse AGM. Freshly isolated PSCs were adept at forming blood vessels with CD31+ luminal endothelium enveloped by PDGFRB+ pericytes, when transplanted subcutaneously into mice. Conditional ablation of PDGFRA+ or Nestin+ cells led to either complete or partial loss of PSCs respectively, with severe loss of endothelial and pericyte-like cells, and concomitant loss of blood formation in the AGM. Lineage tracing studies using tamoxifen induction in PDGFRACreERT2/R26eYFP embryos showed that stromal, sub-endothelial, endothelial and long-term repopulating hematopoietic stem cells (LT-HSCs) cells in the E11.5 AGM were progeny of PDGFRA cells. Using transgenic reporter mice, we showed that MesP1 (mesoderm) derived PDGFRA+ cells dominated the sub-endothelial and deeper ventral stroma in the AGM at E10.5 and E11.5 but were replaced by Wnt1 (neural crest) derived cells at E13.5. Re-aggregation of E11.5 Mesp1 derived PSC cells with E13.5 aortic or adult cardiac non-hemogenic endothelial cells resulted in the generation of endothelial cell derived LT-HSCs. RNA-sequencing analysis of non-hemogenic E13.5 endothelial cells showed up-regulation of EHT genes, WNT, BMP and Notch cell signalling pathways when re-aggregated with E11.5 Mesp1 derived PSCs. LT-HSC generation from these re-aggregates was suppressed by dose-dependent inhibition of PDGF-AA/PDGFRA signalling. Taken together, we report that PSC populations in the AGM are temporally dynamic, and that MesP1-derived PSCs regulate hemogenic potential of the endothelium and that this cooperativity is dependent on PDGF-AA/PDGFRA signalling. This submission represents the RNAseq component of the study.
2022-04-26 | GSE114464 | GEO
Project description:Mesoderm-Derived PDGFRA+ Cells Regulate the Emergence of Hematopoietic Stem Cells in the Dorsal Aorta
| PRJNA687478 | ENA
Project description:Single cell RNA-Seq exploration of the human dorsal aorta, the hematopoietic stem cell (HSC) developmental niche, to explore heterogeneity of the HSC microenvironment and elucidate lineage trajectories of nascent hematopoietic stem/progenitor cells (HSPCs) from endothelium.
2020-09-17 | GSE151876 | GEO
Project description:This dataset contains RNA-Seq data for sorted hematoendothelial subpopulations from the ventral (AoV) and dorsal (AoV) portions of the CS15-16 human embryo dorsal aorta. This includes endothelial (VC+CD45-), Hematopoietic Stem/Progenitor Cells (VC+CD45+) and more mature hematopoietic cells (VC-CD45+) from both the AoV and AoD.
2020-09-17 | GSE151874 | GEO
Project description:The first hematopoietic stem cells originate from hemogenic endothelium (HE), that trans-differentiate into the lumen to form hematopoietic clusters. The molecular mechanisms driving this transition are only poorly understood. Here, we performed single cell RNA-seq profiling of HE cells utilising a RUNX1 and GFI1 reporter mouse line.This allowed for a detailed characterisation of HE cells during endothelial-to-hematopoietic transition. Additionally we profiled the cells surrounding the dorsal aorta. These dataset present a comprehensive profile at single cell resolution of cells invovled in the endothelial-to-hematopoietic transition and the surrounding dorsal aorta niche.
2021-09-21 | GSE150412 | GEO
Project description:Screening for genes regulated by Etv2 within Flk-1+/PDGFRa+ ES derived mesoderm.Microarray analysis performed to screen for the candidate genes regulated by Etv2. TT2 ES cells differentiated on OP9 feeder cells were sorted using Flk-1 and PDGFRa antibodies.Gene expressions from these two populations were compared. Extract RNA from sorted Flk-1+/PDGFRa+ populations from Etv2Het vs KO cells. To obtain primitive mesoderm cells TT2 ES cells of corresponding genotypes were differentiated on OP9 cells for 4 days. Flk-1+/PDGFRa+ populations were sorted from Etv2 Het vs. KO cells for RNA extraction.
2011-08-30 | E-GEOD-31744 | biostudies-arrayexpress
Project description:Mouse dorsal aorta from E9.5 mouse embryos (C57BL6) was grown as an explant culture as described elsewhere (De Angelis et al., 1999). After 5 days the explant was dissociated into a single cell suspension, and plated at limiting dilution on a feeder layer of Mitomycin C-treated primary embryonic mouse fibroblasts, in 96 multiwell plates in complete medium, RPMI 20% Fetal Calf Serum. After 1 week, mesangioblast clones appeared approximately 2-4% of the wells. When the clones had grown to approximately 103 cells they were passed on gelatin-coated dishes, and further expanded. Clones D16 and D351 were used for microarray analysis.
2008-06-13 | E-GEOD-552 | biostudies-arrayexpress
Project description:Mouse dorsal aorta from E9.5 mouse embryos (C57BL6) was grown as an explant culture as described elsewhere (De Angelis et al., 1999). After 5 days the explant was dissociated into a single cell suspension, and plated at limiting dilution on a feeder layer of Mitomycin C-treated primary embryonic mouse fibroblasts, in 96 multiwell plates in complete medium, RPMI 20% Fetal Calf Serum. After 1 week, mesangioblast clones appeared approximately 2-4% of the wells. When the clones had grown to approximately 103 cells they were passed on gelatin-coated dishes, and further expanded. Clones D16 and D351 were used for microarray analysis.
2008-06-13 | E-GEOD-554 | biostudies-arrayexpress
Project description:Development of the dorsal aorta is a key step in the establishment of the adult blood-forming system, since hematopoietic stem and progenitor cells (HSPCs) arise from ventral aortic endothelium in all vertebrate animals studied. Work in zebrafish has demonstrated that arterial and venous endothelial precursors arise from distinct subsets of lateral plate mesoderm. Here, we profile the transcriptome of the earliest detectable endothelial cells (ECs) during zebrafish embryogenesis to demonstrate that tissue-specific EC programs initiate much earlier than previously appreciated, by the end of gastrulation. Classic studies in the chick embryo showed that paraxial mesoderm generates a subset of somite-derived endothelial cells (SDECs) that incorporate into the dorsal aorta to replace HSPCs as they exit the aorta and enter circulation. We describe a conserved program in the zebrafish, where a rare population of endothelial precursors delaminates from the dermomyotome to incorporate exclusively into the developing dorsal aorta. Whereas SDECs lack hematopoietic potential, they act as a local niche to support the emergence of HSPCs from neighboring hemogenic endothelium. Thus, at least three subsets of ECs contribute to the developing dorsal aorta: vascular ECs, hemogenic ECs, and SDECs. Taken together, our findings indicate that the distinct spatial origins of endothelial precursors dictate different cellular potentials within the developing dorsal aorta.
2023-08-01 | E-MTAB-13196 | biostudies-arrayexpress