TY - JOUR
T1 - In Vitro Derivation and Propagation of Spermatogonial Stem Cell Activity from Mouse Pluripotent Stem Cells
AU - Ishikura, Yukiko
AU - Yabuta, Yukihiro
AU - Ohta, Hiroshi
AU - Hayashi, Katsuhiko
AU - Nakamura, Tomonori
AU - Okamoto, Ikuhiro
AU - Yamamoto, Takuya
AU - Kurimoto, Kazuki
AU - Shirane, Kenjiro
AU - Sasaki, Hiroyuki
AU - Saitou, Mitinori
N1 - Publisher Copyright:
© 2016 The Author(s)
PY - 2016/12/6
Y1 - 2016/12/6
N2 - The in vitro derivation and propagation of spermatogonial stem cells (SSCs) from pluripotent stem cells (PSCs) is a key goal in reproductive science. We show here that when aggregated with embryonic testicular somatic cells (reconstituted testes), primordial germ cell-like cells (PGCLCs) induced from mouse embryonic stem cells differentiate into spermatogonia-like cells in vitro and are expandable as cells that resemble germline stem cells (GSCs), a primary cell line with SSC activity. Remarkably, GSC-like cells (GSCLCs), but not PGCLCs, colonize adult testes and, albeit less effectively than GSCs, contribute to spermatogenesis and fertile offspring. Whole-genome analyses reveal that GSCLCs exhibit aberrant methylation at vulnerable regulatory elements, including those critical for spermatogenesis, which may restrain their spermatogenic potential. Our study establishes a strategy for the in vitro derivation of SSC activity from PSCs, which, we propose, relies on faithful epigenomic regulation.
AB - The in vitro derivation and propagation of spermatogonial stem cells (SSCs) from pluripotent stem cells (PSCs) is a key goal in reproductive science. We show here that when aggregated with embryonic testicular somatic cells (reconstituted testes), primordial germ cell-like cells (PGCLCs) induced from mouse embryonic stem cells differentiate into spermatogonia-like cells in vitro and are expandable as cells that resemble germline stem cells (GSCs), a primary cell line with SSC activity. Remarkably, GSC-like cells (GSCLCs), but not PGCLCs, colonize adult testes and, albeit less effectively than GSCs, contribute to spermatogenesis and fertile offspring. Whole-genome analyses reveal that GSCLCs exhibit aberrant methylation at vulnerable regulatory elements, including those critical for spermatogenesis, which may restrain their spermatogenic potential. Our study establishes a strategy for the in vitro derivation of SSC activity from PSCs, which, we propose, relies on faithful epigenomic regulation.
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U2 - 10.1016/j.celrep.2016.11.026
DO - 10.1016/j.celrep.2016.11.026
M3 - Article
C2 - 27926879
AN - SCOPUS:85002954805
VL - 17
SP - 2789
EP - 2804
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 10
ER -