Differentiation of male human embryonic stem cells into germ cell-like cells

Abstract

Studying human germ cell development has presented many challenges with few relevant models and a lack of primary tissue sources. Embryonic stem cells (ESCs) have recently shown great potential as a viable model producing sperm- and oocyte-like cells that in some cases can even produce live offspring. Additionally, it has been established ESC derived germ-like cells respond appropriately to germ cell signaling, express germ cell markers and undergo meiotic division, further confirming their potential as a developmental model. Beyond basic developmental questions, human germ cells might be used in toxicology, drug screening and cell therapy for infertile couples. However, there are still several major challenges facing the field including heterogeneous populations of differentiated cells, the lack of definitive biomarkers, aberrant developmental timing and potential problems caused by the absence of somatic tissue. The field has major hurdles to overcome, yet ESCs are a key tool to use in unlocking the basic elements of germ cell development that may lead to new fertility treatments. The objectives of these studies were to 1) develop a human ESC differentiation culture system capable of producing homogeneous populations of germ cells, 2) explore the role of mouse embryonic fibroblast and basic fibroblast growth factor in enriching and differentiating these cells, 3) determine the ability of these cells to be maintained in extended culture and 4) to study human germ cell developmental signaling.