Accession |
PRJCA002301 |
Title |
Overcoming intrinsic H3K27me3 imprinting barriers improves somatic cell nuclear transfer |
Relevance |
Model organism |
Data types |
Transcriptome or Gene expression
|
Organisms |
Mus musculus
|
Description |
Overcoming critical epigenetic barriers is essential for successful animal cloning by somatic cell nuclear transfer (SCNT). Genomic imprinting is resistant during SCNT reprogramming, so it is not regarded as an epigenetic barrier for cloning. Here, we confirmed that the H3K27me3-dependent imprinting genes (Sfmbt2, Jade1, Gab1, and Smoc1) had intrinsic loss of imprint in the placentae of SCNT embryos. Using a sophisticated approach that combined mouse haploid embryonic stem cells and gene-editing techniques, we successfully produced somatic cells that carried simultaneous monoallelic deletions of four H3K27me3 imprinting genes. Most importantly, the engineered quadruple monoallelic gene deletions that mimicked H3K27me3-imprinted expression patterns significantly increased fibroblast cloning efficiency up to 14.2% (0 for WT fibroblasts) and prevented longstanding placenta- and body-overgrowth defects in cloned animals. |
Sample scope |
Monoisolate |
Release date |
2020-06-18 |
Publication |
PubMed ID |
Article title |
Journal name |
DOI |
Year |
32559418
|
Overcoming Intrinsic H3K27me3 Imprinting Barriers Improves Post-implantation Development after Somatic Cell Nuclear Transfer
|
Cell Stem Cell
|
10.1016/j.stem.2020.05.014
|
2020
|
|
Grants |
Agency |
program |
Grant ID |
Grant title |
Chinese Academy of Sciences (CAS)
|
Strategic Priority Research Program of Chinese Academy of Sciences (CAS)
|
XDA16030403
|
|
|
Submitter |
Guihai
Feng (fenggh@aliyun.com)
|
Organization |
Institute of Zoology, Chinese Academy of Sciences |
Submission date |
2020-02-28 |