Int J Stem Cells.  2020 Jul;13(2):202-211. 10.15283/ijsc20033.

Overexpression of p21 Has Inhibitory Effect on Human Hematopoiesis by Blocking Generation of CD43+ Cells via Cell-Cycle Regulation

Affiliations
  • 1Research Center for Stem Cell Therapies, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu, China
  • 2State Key Laboratory of Biotherapy, Sichuan University, Chengdu, China
  • 3State Key Laboratory of Experimental Hematology, CAMS & PUMC, Tianjin, China

Abstract

Background and Objectives
p21, an important member of the Cip/Kip family, is involved in inhibitory effects of RUNX1b overexpression during the early stage of human hematopoiesis.
Methods and Results
We established a human embryonic stem cell (hESC) line with inducible expression of p21 (p21/hESCs). Overexpression of p21 did not influence either mesoderm induction or emergence of CD34+ cells, but it significantly decreased the production of CD43+ cells and changed the expression profile of hematopoiesis-related factors, leading to the negative effects of p21 on hematopoiesis.
Conclusions
In RUNX1b/hESC co-cultures when RUNX1b was induced from D0, perturbation of the cell cycle caused by upregulation of p21 probably prevented the appearance of CD43+ cells, but not CD34+ cells. The mechanisms via which CD34+ cells are blocked by RUNX1b overexpression remain to be elucidated.

Keyword

p21; RUNX1; CD43; Hematopoiesis; hPSC; AGM-S3; Inducible expression; PiggyBac; Cell cycle
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