Retinoic Acid Promotes Endothelial Cell Cycle Early G1 State to Enable Human Hemogenic Endothelial Cell Specification
Year: 2020
Type: article
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.
Source: Cell Reports
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,200
Funders: U.S. Department of Veterans Affairs, Connecticut Innovations, Svenska Sällskapet för Medicinsk Forskning, National Institutes of Health, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Biomedical Imaging and Bioengineering
Awards: G1045705519, G1119858749, G1324121952, G1546226587, G2697474737, G273984810, G3560987344, miR-223 regulates endothelial to hematopoietic transition, G4305949640, Integrated heart-liver-vascular systems for drug testing in human health and dise, G4556456335, G4764383057, G54061017, G5600156336, G6537541447, G6676706990, Tumor and Immune Programming of Tumor-AssociatedEndothelium, miR-223 regulates endothelial to hematopoietic transition, Endothelial Cell Cycle State and Cell Fate, Specification of Hemogenic Endothelial Cells, G8750114881, G9000113090, Intestinal Lymphocyte Trafficking, Progenitor Cells for High Endothelium in the Immune Response, G932935081
OpenAlex ID: W3020663384