重编程
KLF4公司
染色质
诱导多能干细胞
细胞生物学
体细胞
生物
胚胎干细胞
细胞
干细胞
遗传学
癌症研究
细胞培养
转录因子
细胞分化
体细胞核移植
基因
作者
Yuting Liu,Jiangping He,Ruhai Chen,Li He,Jocelyn Chen,Yujian Liu,Bo Wang,Lin Guo,Duanqing Pei,Jie Wang,Jing Liu,Jiekai Chen
标识
DOI:10.1007/s00018-021-03883-x
摘要
Human induced pluripotent stem cells (iPSCs) technology has been widely applied to cell regeneration and disease modeling. However, most mechanism of somatic reprogramming is studied on mouse system, which is not always generic in human. Consequently, the generation of human iPSCs remains inefficient. Here, we map the chromatin accessibility dynamics during the induction of human iPSCs from urine cells. Comparing to the mouse system, we found that the closing of somatic loci is much slower in human. Moreover, a conserved AP-1 motif is highly enriched among the closed loci. The introduction of AP-1 repressor, JDP2, enhances human reprogramming and facilitates the reactivation of pluripotent genes. However, ESRRB, KDM2B and SALL4, several known pluripotent factors promoting mouse somatic reprogramming fail to enhance human iPSC generation. Mechanistically, we reveal that JDP2 promotes the closing of somatic loci enriching AP-1 motifs to enhance human reprogramming. Furthermore, JDP2 can rescue reprogramming deficiency without MYC or KLF4. These results indicate AP-1 activity is a major barrier to prevent chromatin remodeling during somatic cell reprogramming.
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