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

Publication date: 4 April 2017
Source:Cell Reports, Volume 19, Issue 1
Author(s): Carolina Guibentif, Roger Emanuel Rönn, Charlotta Böiers, Stefan Lang, Shobhit Saxena, Shamit Soneji, Tariq Enver, Göran Karlsson, Niels-Bjarne Woods
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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Teaser

Molecular understanding of the developmental process of endothelial-to-hematopoietic transition (EHT) is critical for ultimately deriving transplantable hematopoietic stem cells from human pluripotent stem cells (hPSCs). Guibentif et al. provide a single-cell transcriptional characterization of this process using hPSC-derived cultures, revealing hematopoietic sublineage restriction before completion of EHT.


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