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Publication : Iterative Single-Cell Analyses Define the Transcriptome of the First Functional Hematopoietic Stem Cells.

First Author  Vink CS Year  2020
Journal  Cell Rep Volume  31
Issue  6 Pages  107627
PubMed ID  32402290 Mgi Jnum  J:306182
Mgi Id  MGI:6715297 Doi  10.1016/j.celrep.2020.107627
Citation  Vink CS, et al. (2020) Iterative Single-Cell Analyses Define the Transcriptome of the First Functional Hematopoietic Stem Cells. Cell Rep 31(6):107627
abstractText  Whereas hundreds of cells in the mouse embryonic aorta transdifferentiate to hematopoietic cells, only very few establish hematopoietic stem cell (HSC) identity at a single time point. The Gata2 transcription factor is essential for HSC generation and function. In contrast to surface-marker-based cell isolation, Gata2-based enrichment provides a direct link to the internal HSC regulatory network. Here, we use iterations of index-sorting of Gata2-expressing intra-aortic hematopoietic cluster (IAHC) cells, single-cell transcriptomics, and functional analyses to connect HSC identity to specific gene expression. Gata2-expressing IAHC cells separate into 5 major transcriptomic clusters. Iterative analyses reveal refined CD31, cKit, and CD27 phenotypic parameters that associate specific molecular profiles in one cluster with distinct HSC and multipotent progenitor function. Thus, by iterations of single-cell approaches, we identify the transcriptome of the first functional HSCs as they emerge in the mouse embryo and localize them to aortic clusters containing 1-2 cells.
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