Primate Primordial Germ Cells Acquire Transplantation Potential by Carnegie Stage 23

Amander T Clark; Sofia Gkountela; Di Chen; Wanlu Liu; Enrique Sosa; Meena Sukhwani; Jon D Hennebold; Kyle E Orwig

doi:10.1016/j.stemcr.2017.05.002

Primate Primordial Germ Cells Acquire Transplantation Potential by Carnegie Stage 23

Stem Cell Reports. 2017 Jul 11;9(1):329-341. doi: 10.1016/j.stemcr.2017.05.002. Epub 2017 Jun 1.

Authors

Amander T Clark¹, Sofia Gkountela², Di Chen³, Wanlu Liu⁴, Enrique Sosa³, Meena Sukhwani⁵, Jon D Hennebold⁶, Kyle E Orwig⁵

Affiliations

¹ Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: clarka@ucla.edu.
² Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA.
³ Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁴ Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁵ Department of Obstetrics, Gynecology and Reproductive Sciences and Magee-Womens Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
⁶ Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Beaverton, OR 97006, USA; Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, OR 97239, USA.

Abstract

Primordial germ cells (PGCs) are the earliest embryonic progenitors in the germline. Correct formation of PGCs is critical to reproductive health as an adult. Recent work has shown that primate PGCs can be differentiated from pluripotent stem cells; however, a bioassay that supports their identity as transplantable germ cells has not been reported. Here, we adopted a xenotransplantation assay by transplanting single-cell suspensions of human and nonhuman primate embryonic Macaca mulatta (rhesus macaque) testes containing PGCs into the seminiferous tubules of adult busulfan-treated nude mice. We discovered that both human and nonhuman primate embryonic testis are xenotransplantable, generating colonies while not generating tumors. Taken together, this work provides two critical references (molecular and functional) for defining transplantable primate PGCs. These results provide a blueprint for differentiating pluripotent stem cells to transplantable PGC-like cells in a species that is amenable to transplantation and fertility studies.

Keywords: PGC; primordial-germ-cell; transplant; xenotransplant.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Busulfan / therapeutic use
Female
Germ Cells / transplantation*
Humans
Immunosuppressive Agents / therapeutic use
Macaca mulatta
Male
Mice, Nude
Seminiferous Tubules / surgery*
Testis / embryology*
Testis / transplantation*
Transplantation, Heterologous / methods

Substances

Immunosuppressive Agents
Busulfan

Abstract

Publication types

MeSH terms

Substances

Grants and funding