ABSTRACT
Primordial germ cells (PGCs) are the embryonic precursors of sperm and eggs. They transmit genetic and epigenetic information across generations. Given the prominent role of germline defects in diseases such as infertility, detailed understanding of human PGC (hPGC) development has important implications in reproductive medicine and studying human evolution. Yet, hPGC specification remains an elusive process. Here, we report the induction of hPGC-like cells (hPGCLCs) in a bioengineered human pluripotent stem cell (hPSC) culture that mimics peri-implantation human development. In this culture, amniotic ectoderm-like cells (AMLCs), derived from hPSCs, induce hPGCLC specification from hPSCs through paracrine signaling downstream of ISL1. Our data further show functional roles of NODAL, WNT, and BMP signaling in hPGCLC induction. hPGCLCs are successfully derived from eight non-obstructive azoospermia (NOA) participant-derived hPSC lines using this biomimetic platform, demonstrating its promise for screening applications.
Subject(s)
Pluripotent Stem Cells , Semen , Humans , Male , Germ Cells/metabolism , Cell Line , Signal Transduction , Cell DifferentiationABSTRACT
We generated and characterized a rhesus macaque induced pluripotent stem cell (iPSC) line using induced reprogramming of fibroblasts isolated from a rhesus macaque fetus. The fibroblasts were expanded and then reprogrammed using non-integrating Sendai virus technology. This line is available as riPSC05. The authenticity of riPSC05 was confirmed through the expression of pluripotent and self-renewal markers, in vitro-directed differentiation towards three germ layers (ectoderm, mesoderm, and endoderm), karyotyping, and STR analysis.
