Sperm ‘grown’ from skin offers hope to infertile men

Direct Differentiation of Human Pluripotent Stem Cells into Haploid Spermatogenic Cells.Human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) have been shown to differentiate into primordial germ cells (PGCs) but not into spermatogonia, haploid spermatocytes, or spermatids. Here, we show that hESCs and hiPSCs differentiate directly into advanced male germ cell lineages, including postmeiotic, spermatid-like cells, in vitro without genetic manipulation. Furthermore, our procedure mirrors spermatogenesis in vivo by differentiating PSCs into UTF1-, PLZF-, and CDH1-positive spermatogonia-like cells; HIWI- and HILI-positive spermatocyte-like cells; and haploid cells expressing acrosin, transition protein 1, and protamine 1 (proteins that are uniquely found in spermatids and/or sperm). These spermatids show uniparental genomic imprints similar to those of human sperm on two loci: H19 and IGF2. These results demonstrate that male PSCs have the ability to differentiate directly into advanced germ cell lineages and may represent a novel strategy for studying

spermatogenesis in vitro. º In vitro culture induces germ cell differentiation of hPSCs º hPSCs differentiate into spermatogonia, spermatocytes, and haploid spermatids º Haploid spermatids have uniparental imprints similar to fertile human sperm Understanding human gametogenesis is vital for improving infertility therapies and contraceptives. Patient-specific stem cells undergoing gametogenesis in vitro represent innovative models for mechanistic investigations and potential therapies. Here, Easley and colleagues show that human embryonic and induced pluripotent stem cells differentiate into advanced germ cell lineages including spermatogonia, spermatocytes, and haploid spermatids with parent-of-origin genomic imprints similar to fertile human sperm. Developing an in vitro spermatogenesis model may prove critical for understanding the mechanistic causes of male infertility. Authors: Charles A. Easley, Bart T. Phillips, Megan M. McGuire, Jennifer M. Barringer, Hanna Valli, Brian P. Hermann, Calvin R. Simerly, Aleksander Rajkovic, Toshio Miki, Kyle E. Orwig, Gerald P. Schatten. –  Affiliations: Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA 15108, USAMagee-Womens Research Institute, Pittsburgh Development Center, Pittsburgh, PA 15108, USADepartment of Biology, University of Texas at San Antonio, San Antonio, TX 78249, USABroad CIRM Center, University of Southern California, Los Angeles, CA 90033, USACorresponding authorPresent address: Laboratory of Translational Cell Biology, Department of Cell Biology, Emory University School of Medicine, Atlanta. Sources:  Cell Reports

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