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J Exp Med. 2018 Feb 5;215(2):645-659. doi: 10.1084/jem.20161594. Epub 2017 Dec 27.

Maturation of hematopoietic stem cells from prehematopoietic stem cells is accompanied by up-regulation of PD-L1.

Author information

1
Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA.
2
Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA.
3
Department of Pediatrics, University of Pennsylvania, Philadelphia, PA.
4
Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA.
5
Department of Biomedical Engineering, University of Iowa, Iowa City, IA.
6
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
7
Department of Pediatrics, University of Washington, Seattle, WA.
8
Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA tank1@email.chop.edu.
9
Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA nancyas@mail.med.upenn.edu.

Abstract

Hematopoietic stem cells (HSCs) mature from pre-HSCs that originate in the major arteries of the embryo. To identify HSCs from in vitro sources, it will be necessary to refine markers of HSCs matured ex vivo. We purified and compared the transcriptomes of pre-HSCs, HSCs matured ex vivo, and fetal liver HSCs. We found that HSC maturation in vivo or ex vivo is accompanied by the down-regulation of genes involved in embryonic development and vasculogenesis, and up-regulation of genes involved in hematopoietic organ development, lymphoid development, and immune responses. Ex vivo matured HSCs more closely resemble fetal liver HSCs than pre-HSCs, but are not their molecular equivalents. We show that ex vivo-matured and fetal liver HSCs express programmed death ligand 1 (PD-L1). PD-L1 does not mark all pre-HSCs, but cell surface PD-L1 was present on HSCs matured ex vivo. PD-L1 signaling is not required for engraftment of embryonic HSCs. Hence, up-regulation of PD-L1 is a correlate of, but not a requirement for, HSC maturation.

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