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Single-Cell Analysis Identifies Distinct Stages of Human Endothelial-to-Hematopoietic Transition

Guibentif, Carolina LU ; Rönn, Roger Emanuel LU ; Böiers, Charlotta LU ; Lang, Stefan LU ; Saxena, Shobhit LU ; Soneji, Shamit LU ; Enver, Tariq LU ; Karlsson, Göran LU and Woods, Niels-Bjarne LU (2017) In Cell Reports 19(1). p.10-19
Abstract

During development, hematopoietic cells originate from endothelium in a process known as endothelial-to-hematopoietic transition (EHT). To study human EHT, we coupled flow cytometry and single-cell transcriptional analyses of human pluripotent stem cell-derived CD34(+) cells. The resulting transcriptional hierarchy showed a continuum of endothelial and hematopoietic signatures. At the interface of these two signatures, a unique group of cells displayed both an endothelial signature and high levels of key hematopoietic stem cell-associated genes. This interphase group was validated via sort and subculture as an immediate precursor to hematopoietic cells. Differential expression analyses further divided this population into subgroups,... (More)

During development, hematopoietic cells originate from endothelium in a process known as endothelial-to-hematopoietic transition (EHT). To study human EHT, we coupled flow cytometry and single-cell transcriptional analyses of human pluripotent stem cell-derived CD34(+) cells. The resulting transcriptional hierarchy showed a continuum of endothelial and hematopoietic signatures. At the interface of these two signatures, a unique group of cells displayed both an endothelial signature and high levels of key hematopoietic stem cell-associated genes. This interphase group was validated via sort and subculture as an immediate precursor to hematopoietic cells. Differential expression analyses further divided this population into subgroups, which, upon subculture, showed distinct hematopoietic lineage differentiation potentials. We therefore propose that immediate precursors to hematopoietic cells already have their hematopoietic lineage restrictions defined prior to complete downregulation of the endothelial signature. These findings increase our understanding of the processes of de novo hematopoietic cell generation in the human developmental context.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cell Reports
volume
19
issue
1
pages
10 pages
publisher
Cell Press
external identifiers
  • scopus:85016965185
  • wos:000398231800002
ISSN
2211-1247
DOI
10.1016/j.celrep.2017.03.023
language
English
LU publication?
yes
id
007862e8-135c-422e-8a64-bd8c089b5ad3
date added to LUP
2017-04-08 09:17:36
date last changed
2017-09-18 13:31:48
@article{007862e8-135c-422e-8a64-bd8c089b5ad3,
  abstract     = {<p>During development, hematopoietic cells originate from endothelium in a process known as endothelial-to-hematopoietic transition (EHT). To study human EHT, we coupled flow cytometry and single-cell transcriptional analyses of human pluripotent stem cell-derived CD34(+) cells. The resulting transcriptional hierarchy showed a continuum of endothelial and hematopoietic signatures. At the interface of these two signatures, a unique group of cells displayed both an endothelial signature and high levels of key hematopoietic stem cell-associated genes. This interphase group was validated via sort and subculture as an immediate precursor to hematopoietic cells. Differential expression analyses further divided this population into subgroups, which, upon subculture, showed distinct hematopoietic lineage differentiation potentials. We therefore propose that immediate precursors to hematopoietic cells already have their hematopoietic lineage restrictions defined prior to complete downregulation of the endothelial signature. These findings increase our understanding of the processes of de novo hematopoietic cell generation in the human developmental context.</p>},
  author       = {Guibentif, Carolina and Rönn, Roger Emanuel and Böiers, Charlotta and Lang, Stefan and Saxena, Shobhit and Soneji, Shamit and Enver, Tariq and Karlsson, Göran and Woods, Niels-Bjarne},
  issn         = {2211-1247},
  language     = {eng},
  month        = {04},
  number       = {1},
  pages        = {10--19},
  publisher    = {Cell Press},
  series       = {Cell Reports},
  title        = {Single-Cell Analysis Identifies Distinct Stages of Human Endothelial-to-Hematopoietic Transition},
  url          = {http://dx.doi.org/10.1016/j.celrep.2017.03.023},
  volume       = {19},
  year         = {2017},
}