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

Jiahui Zeng; Huifang Zhang; Yuanling Liu; Wencui Sun; Danying Yi; Lijiao Zhu; Yonggang Zhang; Xu Pan; Yijing Chen; Ya Zhou; Guohui Bian; Mowen Lai; Qiongxiu Zhou; Jiaxin Liu; Bo Chen; Feng Ma

doi:10.15283/ijsc20033

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

Int J Stem Cells. 2020 Jul 30;13(2):202-211. doi: 10.15283/ijsc20033.

Authors

Jiahui Zeng¹, Huifang Zhang¹, Yuanling Liu¹, Wencui Sun¹, Danying Yi¹, Lijiao Zhu¹, Yonggang Zhang¹, Xu Pan¹, Yijing Chen¹, Ya Zhou¹, Guohui Bian¹, Mowen Lai¹, Qiongxiu Zhou¹, Jiaxin Liu¹, Bo Chen¹, Feng Ma^{1

2

3}

Affiliations

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

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