Open AccessDerivation of male germ cells from induced pluripotent stem cells in vitro and in reconstituted seminiferous tubules
Author(s) -
Yang S.,
Bo J.,
Hu H.,
Guo X.,
Tian R.,
Sun C.,
Zhu Y.,
Li P.,
Liu P.,
Zou S.,
Huang Y.,
Li Z.
Publication year - 2012
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/j.1365-2184.2012.00811.x
Subject(s) - germ cell , embryoid body , induced pluripotent stem cell , biology , microbiology and biotechnology , p19 cell , stem cell , germ line development , embryonic stem cell , genetics , gene
Objectives Previous studies have demonstrated that mouse‐ and human‐induced pluripotent stem (i PS ) cells can differentiate into primordial germ cells in vitro . However, up to now it is not known whether i PS cells would be able to differentiate into male germ cells in vivo . The aim of this study was to explore differentiation potential of i PS cells to male germ cells in vitro and in vivo . Materials and methods In this study, approaches using in vitro retinoic acid induction and in vivo ectopic transplantation were combined to induce i PS cells to become male germ cells. Results RT ‐ PCR showed that expression of pre‐meiotic and meiotic germ cell‐specific genes was enhanced in i PS cell‐derived embryoid bodies ( EB s) compared to m RNA transcripts of iPS cells. Immunofluorescence analysis revealed that iPS cell‐derived EBs positively expressed germ‐cell markers VASA , c‐Kit and SCP 3. Furthermore, i PS cell‐derived cells dissociated from EB s were injected with testicular cells into dorsal skin of mice. Histological examination showed that i PS cell‐derived cells could reconstitute seminiferous tubules, and meanwhile, i PS cell‐derived germ cells could settle at basement membranes of reconstituted tubules. Conclusion Our results suggest that i PS cells are able to differentiate into male germ cells in vitro and that reconstituted seminiferous tubules may provide a functional niche for exogenous i PS cell‐derived male germ cells. Derivation of male germ cells from i PS cells has potential application for treating male infertility and provides an ideal platform for elucidating molecular mechanisms of male germ‐cell development.