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Generation of functional multipotent adult stem cells from GPR125+ germline progenitors
- Source :
- Nature. 449(7160)
- Publication Year :
- 2007
-
Abstract
- Adult mammalian testis is a source of pluripotent stem cells1. However, the lack of specific surface markers has hampered identification and tracking of the unrecognized subset of germ cells that gives rise to multipotent cells2. Although embryonic-like cells can be derived from adult testis cultures after only several weeks in vitro1, it is not known whether adult self-renewing spermatogonia in long-term culture can generate such stem cells as well. Here, we show that highly proliferative adult spermatogonial progenitor cells (SPCs) can be efficiently obtained by cultivation on mitotically inactivated testicular feeders containing CD34+ stromal cells. SPCs exhibit testicular repopulating activity in vivo and maintain the ability in long-term culture to give rise to multi-potent adult spermatogonial-derived stem cells (MASCs). Furthermore, both SPCs and MASCs express GPR125, an orphan adhesion-type G-protein-coupled receptor. In knock-in mice bearing a GPR125–β-galactosidase (LacZ) fusion protein under control of the native Gpr125 promoter (GPR125–LacZ), expression in the testis was detected exclusively in spermatogonia and not in differentiated germ cells. Primary GPR125–LacZ SPC lines retained GPR125 expression, underwent clonal expansion, maintained the phenotype of germline stem cells, and reconstituted spermatogenesis in busulphan-treated mice. Long-term cultures of GPR125+ SPCs (GSPCs) also converted into GPR125+ MASC colonies. GPR125+MASCs generated derivatives of the three germ layers and contributed to chimaeric embryos, with concomitant downregulation of GPR125 during differentiation into GPR125− cells. MASCs also differentiated into contractile cardiac tissue in vitro and formed functional blood vessels in vivo. Molecular book marking by GPR125 in the adult mouse and, ultimately, in the human testis could enrich for a population of SPCs for derivation of GPR125+ MASCs, which may be employed for genetic manipulation, tissue regeneration and revascularization of ischaemic organs.
- Subjects :
- Male
Adult Germline Stem Cells
Aging
Cellular differentiation
Biology
Article
Cell Line
Receptors, G-Protein-Coupled
Mice
Testis
Animals
Regeneration
Progenitor cell
Induced pluripotent stem cell
Busulfan
Multidisciplinary
Gene Expression Profiling
Multipotent Stem Cells
Myocardium
Cell Differentiation
Spermatogonia
Cell biology
Mice, Inbred C57BL
Adult Stem Cells
Cell culture
Multipotent Stem Cell
Immunology
Blood Vessels
Stem cell
Adult stem cell
Subjects
Details
- ISSN :
- 14764687
- Volume :
- 449
- Issue :
- 7160
- Database :
- OpenAIRE
- Journal :
- Nature
- Accession number :
- edsair.doi.dedup.....618bc9e8323f963c3c99386c216f12d8