Open AccessSingle Cell Resolution of Human Hematoendothelial Cells Defines Transcriptional Signatures of Hemogenic Endothelium
Author(s) -
Angelos Mathew G.,
Abrahante Juan E.,
Blum Robert H.,
Kaufman Dan S.
Publication year - 2018
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2739
Subject(s) - biology , gata2 , microbiology and biotechnology , haematopoiesis , embryonic stem cell , induced pluripotent stem cell , stem cell , runx1 , cd34 , cd31 , hemangioblast , progenitor cell , endothelial stem cell , genetics , gene , angiogenesis , in vitro
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 + 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 (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. S tem C ells 2018;36:206–217