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Cell Rep. 2017 Apr 4;19(1):10-19. doi: 10.1016/j.celrep.2017.03.023.

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

Author information

1
Section of Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, BMC A12, 221 84 Lund, Sweden.
2
Division of Molecular Hematology, Lund Stem Cell Center, Lund University, BMC B12, 221 84 Lund, Sweden.
3
Section of Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, BMC A12, 221 84 Lund, Sweden; Stem Cell Laboratory, UCL Cancer Institute, University College London, London W1CE 6BT, UK.
4
Division of Molecular Hematology, Lund Stem Cell Center, Lund University, BMC B12, 221 84 Lund, Sweden. Electronic address: goran.karlsson@med.lu.se.
5
Section of Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, BMC A12, 221 84 Lund, Sweden. Electronic address: niels-bjarne.woods@med.lu.se.

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, 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.

KEYWORDS:

developmental hematopoiesis; endothelial-to-hematopoietic transition; hematopoietic stem cell; human induced pluripotent stem cells; single cell analysis

PMID:
28380349
DOI:
10.1016/j.celrep.2017.03.023
[Indexed for MEDLINE]
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