Direct Conversion from Mouse Fibroblasts Informs the Identification of Hemogenic Precursor Cells In Vivo
Transcriptomics Dataset
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General Information
AccessionGSE54574
TitleDirect Conversion from Mouse Fibroblasts Informs the Identification of Hemogenic Precursor Cells In Vivo
DescriptionDefinitive hematopoiesis emerges via an endothelial-to-hematopoietic transition in the aorta-gonad-mesonephros (AGM) region and placenta. We have recently demonstrated the induction of hematopoietic stem/progenitors (HSPCs) from mouse fibroblasts with a combination of transcription factors progressing through endothelial-like precursors. Here, guided by our in vitro programming experiments we analyzed mouse placentas for the presence of the precursor phenotype. We identified a small population of CD34+ Sca1+Prom1+ (34PS) cells in mid-gestation placentas that do not express the pan-hematopoietic marker CD45. After isolation and culture 34PS cells acquire CD45 and generate large hematopoietic as well as cobblestone colonies. Prom1+ cells localize to the placental vascular labyrinth where HSPCs emerge. 34PS cells express markers associated with the hemogenic endothelium (CD31, Tie2, VE-Cadherin, Sox17, Runx1, Scl) and also markers identified by direct induction (Itga6/CD49f). This population is heterogeneous for the early hematopoietic marker CD41 and expresses the programming transcription factors. Remarkably, global gene expression profiles of placental 34PS cells correlate with AGM-derived hemogenic endothelium and fibroblast-derived precursors. Finally, when co-cultured with stroma placental 34PS cells give rise to B/T lymphoid cells as well as mixed colonies containing erythroid, myeloid and megakaryocytic cell lineages. In summary, we show that direct in vitro conversion provided a cell surface phenotype for the isolation of hemogenic precursors in vivo. Our findings provide insights into the specification of definitive hemogenesis in the placenta, in depth characterization of hemogenic precursor populations and the first evidence that direct in vitro conversion approaches can be used as a valuable tool to address basic developmental questions in vivo.
Landing Pagehttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE54574
RepositoryGene Expression Omnibus
Tools used to analyze the dataset
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ARCHS4
Published September 2017
ARCHS4 provides access to gene counts from HiSeq 2000 and HiSeq 2500 platforms for human and mouse experiments from GEO ...
4645
Clustergrammer
Published October 2017
Web-based tool for visualizing and analyzing high-dimensional data as interactive and shareable heatmaps
4645
Canned Analyses generated with the dataset
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Interactive heatmap visualization of RNA-seq dataset GSE54574
ARCHS4, Clustergrammer
Highly interactive web-based heatmap visualization of the top 500 most variable genes in t...
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