Back

Highly efficient XIST reactivation in female hPSC by transient dual inhibition of TP53 and DNA methylation during Cas9 mediated genome editing

Motosugi, N.; Hasegawa, k.; Kurosaki, N.; Kawaguchi, E.; Izumi, K.; Iida, Y.; Higashiseto, M.; Yokoyama, K.; Sasaki, A.; Nakabayashi, K.; Fukuda, A.

2024-11-06 cell biology
10.1101/2024.11.04.622001 bioRxiv
Show abstract

Erosion of X-chromosome inactivation (XCI) complicates disease and developmental modeling in female human pluripotent stem cells (hPSCs). Previous studies demonstrated that Cas9-mediated editing of the XIST promoter via non-homologous end joining (NHEJ) or homology-directed repair (HDR) with a selection cassette upstream of XIST can trigger DNA demethylation and XIST reactivation, restoring XCI. Here, we show that NHEJ-mediated XCI reacquisition is more stable during differentiation than HDR. We further developed a novel, efficient XIST reactivation method by combining TP53 inhibition with DNA methylation maintenance suppression during Cas9-mediated NHEJ, offering a robust approach to achieving stable XCI in female hPSCs for diverse applications.

Matching journals

The top 2 journals account for 50% of the predicted probability mass.

1
Stem Cell Reports
○ 130 papers in training set
Top 0.1%
46.2%
Similar papers in this journal
2
eLife
● 5828 papers in training set
Top 10%
9.9%
Similar papers in this journal
50% of probability mass above
3
Cell Reports
○ 1498 papers in training set
Top 8%
4.9%
Similar papers in this journal
4
iScience
○ 1154 papers in training set
Top 5%
3.6%
Similar papers in this journal
5
Development
● 497 papers in training set
Top 2%
3.3%
Similar papers in this journal
6
Science Advances
● 1243 papers in training set
Top 10%
3.3%
7
Cell Stem Cell
○ 62 papers in training set
Top 0.6%
2.8%
8
Nature Communications
○ 5641 papers in training set
Top 39%
2.5%
9
Cell Reports Methods
○ 165 papers in training set
Top 2%
1.5%
10
Proceedings of the National Academy of Sciences
● 2444 papers in training set
Top 34%
1.1%
11
Communications Biology
○ 993 papers in training set
Top 20%
1.1%
12
Protein & Cell
◐ 25 papers in training set
Top 0.3%
1.1%
13
The EMBO Journal
○ 309 papers in training set
Top 4%
1.1%
14
Biology Open
● 156 papers in training set
Top 3%
1.1%
15
Nucleic Acids Research
◐ 1281 papers in training set
Top 12%
1.0%
16
EMBO Reports
○ 263 papers in training set
Top 6%
1.0%
17
Stem Cells
◐ 31 papers in training set
Top 0.7%
0.9%
18
Scientific Reports
○ 3612 papers in training set
Top 71%
0.9%
19
Life Science Alliance
● 285 papers in training set
Top 9%
0.6%

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.