puc-header

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

29 Pages Posted: 11 Mar 2020 Sneak Peek Status: Review Complete

See all articles by Jingyao Qiu

Jingyao Qiu

Yale University

Sofia Nordling

Stanford University

Hema Vasavada

Yale University

Eugene Butcher

Stanford University

Karen K. Hirschi

Yale University - Department of Medicine

More...

Abstract

Development of blood-forming (hemogenic) endothelial cells that give rise to hematopoietic stem and progenitor cells (HSPC) is critical during embryogenesis to generate the embryonic and postnatal hematopoietic system. We previously demonstrated that 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 novel protocol to derive endothelial cells, hemogenic endothelial cells and blood cells from human embryonic stem cells. Using this model, we demonstrate that RA and cell cycle control play essential roles in human hemogenic endothelial cell specification. That is, RA promotes endothelial cell cycle arrest to enable RA-induced instructive signals to upregulate hematopoietic gene expression. These novel insights will provide guidance for the ex vivo generation of autologous human HSPC for regenerative medicine applications.

Keywords: Human hemogenic endothelial cell specification, HSPC production, retinoic acid signaling, cell cycle control.

Suggested Citation

Qiu, Jingyao and Nordling, Sofia and Vasavada, Hema and Butcher, Eugene and Hirschi, Karen K., Retinoic Acid Promotes Endothelial Cell Cycle Early G1 State to Enable Human Hemogenic Endothelial Cell Specification. CELL-REPORTS-D-20-00687. Available at SSRN: https://ssrn.com/abstract=3548105 or http://dx.doi.org/10.2139/ssrn.3548105
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Jingyao Qiu

Yale University

New Haven, CT 06520
United States

Sofia Nordling

Stanford University

Stanford, CA 94305
United States

Hema Vasavada

Yale University

New Haven, CT 06520
United States

Eugene Butcher

Stanford University

Stanford, CA 94305
United States

Karen K. Hirschi (Contact Author)

Yale University - Department of Medicine

New Haven, CT
United States

Click here to go to Cell.com

Paper statistics

Abstract Views
87
Downloads
3