Long-term expansion with germline potential of human primordial germ cell-like cells in vitro
© 2020 The Authors..
Human germ cells perpetuate human genetic and epigenetic information. However, the underlying mechanism remains elusive, due to a lack of appropriate experimental systems. Here, we show that human primordial germ cell-like cells (hPGCLCs) derived from human-induced pluripotent stem cells (hiPSCs) can be propagated to at least ~106 -fold over a period of 4 months under a defined condition in vitro. During expansion, hPGCLCs maintain an early hPGC-like transcriptome and preserve their genome-wide DNA methylation profiles, most likely due to retention of maintenance DNA methyltransferase activity. These characteristics contrast starkly with those of mouse PGCLCs, which, under an analogous condition, show a limited propagation (up to ~50-fold) and persist only around 1 week, yet undergo cell-autonomous genome-wide DNA demethylation. Importantly, upon aggregation culture with mouse embryonic ovarian somatic cells in xenogeneic-reconstituted ovaries, expanded hPGCLCs initiate genome-wide DNA demethylation and differentiate into oogonia/gonocyte-like cells, demonstrating their germline potential. By creating a paradigm for hPGCLC expansion, our study uncovers critical divergences in expansion potential and the mechanism for epigenetic reprogramming between the human and mouse germ cell lineage.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:39 |
|---|---|
| Enthalten in: |
The EMBO journal - 39(2020), 21 vom: 02. Nov., Seite e104929 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Murase, Yusuke [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Epigenetic reprogramming |
|---|
| Anmerkungen: |
Date Completed 19.04.2021 Date Revised 03.11.2021 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.15252/embj.2020104929 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM315258446 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM315258446 | ||
| 003 | DE-627 | ||
| 005 | 20231225154523.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.15252/embj.2020104929 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1050.xml |
| 035 | |a (DE-627)NLM315258446 | ||
| 035 | |a (NLM)32954504 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Murase, Yusuke |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Long-term expansion with germline potential of human primordial germ cell-like cells in vitro |
| 264 | 1 | |c 2020 | |
| 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 19.04.2021 | ||
| 500 | |a Date Revised 03.11.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2020 The Authors. | ||
| 520 | |a Human germ cells perpetuate human genetic and epigenetic information. However, the underlying mechanism remains elusive, due to a lack of appropriate experimental systems. Here, we show that human primordial germ cell-like cells (hPGCLCs) derived from human-induced pluripotent stem cells (hiPSCs) can be propagated to at least ~106 -fold over a period of 4 months under a defined condition in vitro. During expansion, hPGCLCs maintain an early hPGC-like transcriptome and preserve their genome-wide DNA methylation profiles, most likely due to retention of maintenance DNA methyltransferase activity. These characteristics contrast starkly with those of mouse PGCLCs, which, under an analogous condition, show a limited propagation (up to ~50-fold) and persist only around 1 week, yet undergo cell-autonomous genome-wide DNA demethylation. Importantly, upon aggregation culture with mouse embryonic ovarian somatic cells in xenogeneic-reconstituted ovaries, expanded hPGCLCs initiate genome-wide DNA demethylation and differentiate into oogonia/gonocyte-like cells, demonstrating their germline potential. By creating a paradigm for hPGCLC expansion, our study uncovers critical divergences in expansion potential and the mechanism for epigenetic reprogramming between the human and mouse germ cell lineage | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a epigenetic reprogramming | |
| 650 | 4 | |a hPGC-like cells | |
| 650 | 4 | |a human primordial germ cells | |
| 650 | 4 | |a in vitro expansion | |
| 650 | 4 | |a oogonia | |
| 700 | 1 | |a Yabuta, Yukihiro |e verfasserin |4 aut | |
| 700 | 1 | |a Ohta, Hiroshi |e verfasserin |4 aut | |
| 700 | 1 | |a Yamashiro, Chika |e verfasserin |4 aut | |
| 700 | 1 | |a Nakamura, Tomonori |e verfasserin |4 aut | |
| 700 | 1 | |a Yamamoto, Takuya |e verfasserin |4 aut | |
| 700 | 1 | |a Saitou, Mitinori |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The EMBO journal |d 1982 |g 39(2020), 21 vom: 02. Nov., Seite e104929 |w (DE-627)NLM012617202 |x 1460-2075 |7 nnns |
| 773 | 1 | 8 | |g volume:39 |g year:2020 |g number:21 |g day:02 |g month:11 |g pages:e104929 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.15252/embj.2020104929 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 39 |j 2020 |e 21 |b 02 |c 11 |h e104929 | ||