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In Vitro Derivation of Human Sperm from Embryonic Stem Cells
Karim Nayernia, Jae Ho Lee, Majlinda Lako, Lyle Armstrong, Mary Herbert, Manyu Li, Wolfgang Engel, David Elliott, Miodrag Stojkovic, John Parrington, Alison Murdoch, Tom Strachan, Xin Zhang
Differentiation of human embryonic stem cells (hESCs) to specific cell types can be achieved using methods that mimic in vivo embryonic developmental programs. Human egg and sperm cells (gametes) are derived from a founder population of germline stem cells (GSCs), primordial germ cells (PGCs), that are set aside early in embryogenesis which give raise to gonocytes in males. After birth, gonocytes differentiate to adult male germline stem cells, spermatogonial stem cells (SSCs), which can self-renew and generate sperm cells, are unique stem cells in that they are solely dedicated to transmit genetic information from generation to generation. Understanding the mechanisms of germ cell specification, development and its differentiation to sperm is important for elucidating the causes of male infertility. Here, we developed an in vitro strategy for establishing of male GSCs from human embryonic stem cells. These in vitro derived GSCs express markers which are specific for PGCs, SSCs, meiotic and postmeiotic germ cells indicating maturation of the primordial germ cells to haploid male gametes. In vitro derived germ cells are able to enter meiosis and generate haploid motile sperm-like cells in vitro. While full potential of the human ES derived germ cells and sperm remains to be demonstrated, this in vitro modeling of human gametogenesis provides a new approach for studying biology of human germ cells and establishment of therapeutic approaches in reproductive medicine.
