2. Academic Validation
  3. Retinoic Acid Promotes Endothelial Cell Cycle Early G1 State to Enable Human Hemogenic Endothelial Cell Specification

Retinoic Acid Promotes Endothelial Cell Cycle Early G1 State to Enable Human Hemogenic Endothelial Cell Specification

  • Cell Rep. 2020 Dec 1;33(9):108465. doi: 10.1016/j.celrep.2020.108465.
Jingyao Qiu 1,  Sofia Nordling 2,  Hema H Vasavada 3,  Eugene C Butcher 4,  Karen K Hirschi 5
Affiliations

Affiliations

  • 1 Department of Medicine, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA; Yale Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT 06520, USA; Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, USA; Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT 06520, USA.
  • 2 Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • 3 Yale Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT 06520, USA.
  • 4 Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Palo Alto Veterans Institute for Research, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA; The Center for Molecular Biology and Medicine, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA.
  • 5 Department of Medicine, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA; Yale Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT 06520, USA; Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, USA; Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Cell Biology, University of Virginia, Charlottesville, VA 22908, USA. Electronic address: kkh4yy@virginia.edu.
PMID: 33264627 DOI: 10.1016/j.celrep.2020.108465
Abstract

Development of blood-forming (hemogenic) endothelial cells that give rise to hematopoietic stem and progenitor cells (HSPCs) is critical during embryogenesis to generate the embryonic and postnatal hematopoietic system. We previously demonstrated that the specification of murine hemogenic endothelial cells is promoted by retinoic acid (RA) signaling and requires downstream endothelial cell cycle control. Whether this mechanism is conserved in human hemogenic endothelial cell specification is unknown. Here, we present a protocol to derive primordial endothelial cells from human embryonic stem cells and promote their specification toward hemogenic endothelial cells. Furthermore, we demonstrate that RA treatment significantly increases human hemogenic endothelial cell specification. That is, RA promotes endothelial cell cycle arrest to enable RA-induced instructive signals to upregulate the genes needed for hematopoietic transition. These insights provide guidance for the ex vivo generation of autologous human hemogenic endothelial cells that are needed to produce human HSPCs for regenerative medicine applications.

Keywords

cell cycle regulation; human hemogenic endothelial cell specification; retinoic acid signaling.

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