Derivation of totipotent-like stem cells with blastocyst-like structure forming potential
© 2022. The Author(s)..
It is challenging to derive totipotent stem cells in vitro that functionally and molecularly resemble cells from totipotent embryos. Here, we report that a chemical cocktail enables the derivation of totipotent-like stem cells, designated as totipotent potential stem (TPS) cells, from 2-cell mouse embryos and extended pluripotent stem cells, and that these TPS cells can be stably maintained long term in vitro. TPS cells shared features with 2-cell mouse embryos in terms of totipotency markers, transcriptome, chromatin accessibility and DNA methylation patterns. In vivo chimera formation assays show that these cells have embryonic and extraembryonic developmental potentials at the single-cell level. Moreover, TPS cells can be induced into blastocyst-like structures resembling preimplantation mouse blastocysts. Mechanistically, inhibition of HDAC1/2 and DOT1L activity and activation of RARγ signaling are important for inducing and maintaining totipotent features of TPS cells. Our study opens up a new path toward fully capturing totipotent stem cells in vitro.
| Errataetall: |
CommentIn: Cell Res. 2022 Aug;32(8):705-706. - PMID 35790810 |
|---|---|
| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:32 |
|---|---|
| Enthalten in: |
Cell research - 32(2022), 6 vom: 04. Juni, Seite 513-529 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Xu, Yaxing [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
|---|
| Anmerkungen: |
Date Completed 03.06.2022 Date Revised 05.11.2022 published: Print-Electronic CommentIn: Cell Res. 2022 Aug;32(8):705-706. - PMID 35790810 Citation Status MEDLINE |
|---|
| doi: |
10.1038/s41422-022-00668-0 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM340371684 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM340371684 | ||
| 003 | DE-627 | ||
| 005 | 20231226005035.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41422-022-00668-0 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1134.xml |
| 035 | |a (DE-627)NLM340371684 | ||
| 035 | |a (NLM)35508506 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Xu, Yaxing |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Derivation of totipotent-like stem cells with blastocyst-like structure forming potential |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 03.06.2022 | ||
| 500 | |a Date Revised 05.11.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a CommentIn: Cell Res. 2022 Aug;32(8):705-706. - PMID 35790810 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022. The Author(s). | ||
| 520 | |a It is challenging to derive totipotent stem cells in vitro that functionally and molecularly resemble cells from totipotent embryos. Here, we report that a chemical cocktail enables the derivation of totipotent-like stem cells, designated as totipotent potential stem (TPS) cells, from 2-cell mouse embryos and extended pluripotent stem cells, and that these TPS cells can be stably maintained long term in vitro. TPS cells shared features with 2-cell mouse embryos in terms of totipotency markers, transcriptome, chromatin accessibility and DNA methylation patterns. In vivo chimera formation assays show that these cells have embryonic and extraembryonic developmental potentials at the single-cell level. Moreover, TPS cells can be induced into blastocyst-like structures resembling preimplantation mouse blastocysts. Mechanistically, inhibition of HDAC1/2 and DOT1L activity and activation of RARγ signaling are important for inducing and maintaining totipotent features of TPS cells. Our study opens up a new path toward fully capturing totipotent stem cells in vitro | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Chromatin |2 NLM | |
| 700 | 1 | |a Zhao, Jingru |e verfasserin |4 aut | |
| 700 | 1 | |a Ren, Yixuan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xuyang |e verfasserin |4 aut | |
| 700 | 1 | |a Lyu, Yulin |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Bingqing |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Yiming |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Xiandun |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Haiyin |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Weifeng |e verfasserin |4 aut | |
| 700 | 1 | |a Fu, Yenan |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yinan |e verfasserin |4 aut | |
| 700 | 1 | |a Mu, Rong |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Cheng |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Deng, Hongkui |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cell research |d 1997 |g 32(2022), 6 vom: 04. Juni, Seite 513-529 |w (DE-627)NLM09215381X |x 1748-7838 |7 nnns |
| 773 | 1 | 8 | |g volume:32 |g year:2022 |g number:6 |g day:04 |g month:06 |g pages:513-529 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1038/s41422-022-00668-0 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 32 |j 2022 |e 6 |b 04 |c 06 |h 513-529 | ||