4 years ago

Single cell resolution of human hemato-endothelial cells defines transcriptional signatures of hemogenic endothelium

Single cell resolution of human hemato-endothelial cells defines transcriptional signatures of hemogenic endothelium
Dan S. Kaufman, Robert H. Blum, Juan E. Abrahante, Mathew G. Angelos
Endothelial-to-hematopoietic transition (EHT) is an important stage in definitive hematopoietic development. However, the genetic mechanisms underlying human EHT remains poorly characterized. We performed single cell RNA-seq using 55 hemogenic endothelial cells (HE: CD31+CD144+CD41-CD43-CD45-CD73-RUNX1c+), 47 vascular endothelial cells without hematopoietic potential (non-HE: CD31+CD144+CD41-CD43-CD45-CD73-RUNX1c-), and 35 hematopoietic progenitor cells (HP: CD34+CD43+RUNX1c+) derived from human embryonic stem cells (hESCs). HE and HP were enriched in genes implicated in hemogenic endothelial transcriptional networks, such as ERG, GATA2, and FLI. We found transcriptional overlap between individual HE and HP cells; however, these populations were distinct from non-HE. Further analysis revealed novel biomarkers for human HE/HP cells, including TIMP3, ESAM, RHOJ, and DLL4. Collectively, we demonstrate that hESC-derived HE and HP share a common developmental pathway, while non-HE are more heterogeneous and transcriptionally distinct. Our findings provide a novel strategy to test new genetic targets and optimize the production of definitive hematopoietic cells from human pluripotent stem cells. This article is protected by copyright. All rights reserved. Using a RUNX1c reporter hESC line, we derived functional hemogenic endothelium, nonhemogenic endothelium, and early hematopoietic progenitor cells from embryoid bodies (EB). With singlecell RNA-sequencing, we characterized the genetic signatures distinct to each population and further identified novel genetic targets that may be used to optimize production of definitive human hematopoietic cells from pluripotent stem cells.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/stem.2739

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