RT Journal Article
SR Electronic
T1 Induce Pluripotency via Specific distal enhancer-promoter associations
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.06.09.447809
DO 10.1101/2021.06.09.447809
A1 Xiusheng Zhu
A1 Lei Huang
A1 Dongwei Li
A1 Jing Luo
A1 Qitong Huang
A1 Xueyan Wang
A1 Yubo Zhang
YR 2021
UL http://biorxiv.org/content/early/2021/06/10/2021.06.09.447809.abstract
AB Induced pluripotent stem cell (iPSC) technology promises to be an inexhaustible source of any type of cell needed for therapeutic and research purposes. It is unclear that how distal enhancer-promoter associations/ 3D chromatin conformation involving in the capacity of self-renewal and pluripotency maintenance. In this study, we have selected a few defined enhancer-promoter associations. After screening of enhancer specificity and activity individually, we design the different combinations and transfect these enhancers into the MEF cells. We simultaneously transfect 7 determined enhancers which represents various specific distal chromatin associations into a GFP tracing MEF cell line. We observe that the MEF cells start generating iPS-like clones at day 22. Importantly, our validations with three germ layer marker genes and in vitro experiments have further confirmed the pluripotency of these clones. Here, our study proposes a potential de novo method of a low-genetic risk iPS generation by introducing spatiotemporal distal chromatin associations. This result also paves out the way on utilizing 3D genomic information to alter cell identity and reprogramming for potential therapeutic strategy.Competing Interest StatementThe authors have declared no competing interest.