Long-term expansion with germline potential of human primordial germ cell-like cells in vitro.
EMBO J
; 39(21): e104929, 2020 11 02.
Article
in En
| MEDLINE
| ID: mdl-32954504
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ovary
/
Pluripotent Stem Cells
/
Germ Cells
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
EMBO J
Year:
2020
Type:
Article
Affiliation country:
Japan