Open AccessGenome stabilization by RAD51‐stimulatory compound 1 enhances efficiency of somatic cell nuclear transfer‐mediated reprogramming and full‐term development of cloned mouse embryos
Author(s) -
Lee Ah Reum,
Park JiHoon,
Shim Sung Han,
Hong Kwonho,
La Hyeonwoo,
Park KyungSoon,
Lee Dong Ryul
Publication year - 2021
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.13059
Subject(s) - somatic cell nuclear transfer , reprogramming , biology , microbiology and biotechnology , somatic cell , chromatin , embryo , transdifferentiation , genome instability , dna damage , genetics , cell , stem cell , blastocyst , embryogenesis , dna , gene
Abstract Objectives The genetic instability and DNA damage arise during transcription factor‐mediated reprogramming of somatic cells, and its efficiency may be reduced due to abnormal chromatin remodelling. The efficiency in somatic cell nuclear transfer (SCNT)‐mediated reprogramming is also very low, and it is caused by development arrest of most reconstituted embryos. Materials and Methods Whether the repair of genetic instability or double‐strand breaks (DSBs) during SCNT reprogramming may play an important role in embryonic development, we observed and analysed the effect of Rad 51 , a key modulator of DNA damage response (DDR) in SCNT‐derived embryos. Results Here, we observed that the activity of Rad 51 is lower in SCNT eggs than in conventional IVF and found a significantly lower level of DSBs in SCNT embryos during reprogramming. To address this difference, supplementation with RS‐1, an activator of Rad51 , during the activation of SCNT embryos can increase RAD51 expression and DSB foci and thereby increased the efficiency of SCNT reprogramming. Through subsequent single‐cell RNA‐seq analysis, we observed the reactivation of a large number of genes that were not expressed in SCNT‐2‐cell embryos by the upregulation of DDR, which may be related to overcoming the developmental block. Additionally, there may be an independent pathway involving histone demethylase that can reduce reprograming‐resistance regions. Conclusions This technology can contribute to the production of comparable cell sources for regenerative medicine.