Reference - Detail
| RRC ID | 85340 |
|---|---|
| Author | Motosugi N, Hasegawa K, Kurosaki N, Kawaguchi E, Izumi K, Iida Y, Higashiseto M, Yokoyama K, Sasaki A, Nakabayashi K, Fukuda A. |
| Title | Highly efficient XIST reactivation in female hPSC by transient dual inhibition of TP53 and DNA methylation during Cas9 mediated genome editing. |
| Journal | Stem Cell Res Ther |
| Abstract |
The irreversible erosion of X-chromosome inactivation (XCI) due to repression of the long non-coding RNA XIST presents a major challenge for disease modeling and raises safety concerns for the clinical application of female human pluripotent stem cells (hPSCs) due to the aberrant overexpression of X-linked genes. While Cas9-mediated non-homologous end joining (NHEJ) targeting the XIST promoter can induce DNA demethylation and restore XCI by reactivating XIST, its efficiency remains low. Here, we introduce a highly efficient strategy for XIST reactivation by combining TP53 inhibition with suppression of DNA methylation maintenance during Cas9-mediated NHEJ. This dual-inhibition approach increased the proportion of XIST-positive hPSCs from ~ 5 to ~ 43.7%, providing a robust method for stabilizing XCI in female hPSCs for diverse applications. |
| Volume | 16(1) |
| Pages | 389 |
| Published | 2025-7-18 |
| DOI | 10.1186/s13287-025-04501-4 |
| PII | 10.1186/s13287-025-04501-4 |
| PMID | 40682144 |
| PMC | PMC12275311 |
| MeSH | CRISPR-Cas Systems* / genetics DNA Methylation* / genetics Female Gene Editing* / methods Humans Pluripotent Stem Cells* / cytology Pluripotent Stem Cells* / metabolism RNA, Long Noncoding* / genetics RNA, Long Noncoding* / metabolism Tumor Suppressor Protein p53* / antagonists & inhibitors Tumor Suppressor Protein p53* / genetics Tumor Suppressor Protein p53* / metabolism X Chromosome Inactivation / genetics |
| IF | 5.116 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 2 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | HPS2478(HPS2478) HPS2508(HPS2508) HPS3131(HPS3131) HPS3676(HPS3676) HPS3681(HPS3681) HPS3686(HPS3686) HPS3692(HPS3692) HPS3696(HPS3696) HPS3810(HPS3810) HPS4115(HPS4115) |