Single Cell Resolution of Human Hematoendothelial Cells Defines Transcriptional Signatures of Hemogenic Endothelium

Mathew G. Angelos, Juan E. Abrahante, Robert H. Blum, Dan S. Kaufman

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Endothelial-to-hematopoietic transition (EHT) is an important stage in definitive hematopoietic development. However, the genetic mechanisms underlying human EHT remain poorly characterized. We performed single cell RNA-seq using 55 hemogenic endothelial cells (HECs: CD31+CD144+CD41CD43CD45CD73RUNX1c+), 47 vascular endothelial cells without hematopoietic potential (non-HE: CD31+CD144+CD41CD43CD45CD73RUNX1c), and 35 hematopoietic progenitor cells (HPCs: 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 HECs and HPCs; however, these populations were distinct from non-HE. Further analysis revealed novel biomarkers for human HEC/HPCs, 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. Stem Cells 2018;36:206–217.

Original languageEnglish (US)
Pages (from-to)206-217
Number of pages12
JournalSTEM CELLS
Volume36
Issue number2
DOIs
StatePublished - Feb 1 2018

Bibliographical note

Funding Information:
We thank Jerry Daniel and the University of Minnesota Genomic Center for technical assistance with the single cell RNASeq and Gene Yeo (UCSD) for helpful discussion. This work was supported by NIH Grants: National Cancer Institute Grant R01CA203348 (to D.S.K.), National Institute of Diabetes and Digestive and Kidney Diseases Grant F30DK107071 (to M.G.A), and National Institute of General Medicine Sciences grant T32GM113846 (to M.G.A and D.S.K.) and T32GM008244 (to M.G.A) as well as the Regenerative Medicine Minnesota program (to D.S.K.).

Funding Information:
We thank Jerry Daniel and the University of Minnesota Genomic Center for technical assistance with the single cell RNA-Seq and Gene Yeo (UCSD) for helpful discussion. This work was supported by NIH Grants: National Cancer Institute Grant R01CA203348 (to D.S.K.), National Institute of Diabetes and Digestive and Kidney Diseases Grant F30DK107071 (to M.G.A), and National Institute of General Medicine Sciences grant T32GM113846 (to M.G.A and D.S.K.) and T32GM008244 (to M.G.A) as well as the Regenerative Medicine Minnesota program (to D.S.K.).

Keywords

  • Hemogenic endothelium
  • Human embryonic stem cells
  • Human hematopoiesis
  • Single cell RNA-seq

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