Zeng Jiahui, Zhang Huifang, Liu Yuanling, Sun Wencui, Yi Danying, Zhu Lijiao, Zhang Yonggang, Pan Xu, Chen Yijing, Zhou Ya, Bian Guohui, Lai Mowen, Zhou Qiongxiu, Liu Jiaxin, Chen Bo, Ma Feng
Research Center for Stem Cell Therapies, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu, China.
State Key Laboratory of Biotherapy, Sichuan University, Chengdu, China.
Int J Stem Cells. 2020 Jul 30;13(2):202-211. doi: 10.15283/ijsc20033.
p21, an important member of the Cip/Kip family, is involved in inhibitory effects of overexpression during the early stage of human hematopoiesis.
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.
In /hESC co-cultures when 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 overexpression remain to be elucidated.
p21是Cip/Kip家族的重要成员,在人类造血早期阶段参与过表达的抑制作用。
我们建立了一种可诱导表达p21的人胚胎干细胞(hESC)系(p21/hESCs)。p21的过表达既不影响中胚层诱导,也不影响CD34+细胞的出现,但它显著降低了CD43+细胞的产生,并改变了造血相关因子的表达谱,导致p21对造血产生负面影响。
在从D0开始诱导p21的/hESC共培养物中,p21上调引起的细胞周期扰动可能阻止了CD43+细胞的出现,但未阻止CD34+细胞的出现。p21过表达阻断CD34+细胞的机制仍有待阐明。