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 Direct Differentiation of Human Pluripotent Stem Cells into Haploid Spermatogenic Cells.The first author is Dr. Charles Easley IV who just accepted a faculty position at Emory University and full authorship is:  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 It is now available online  in CELL Reports at: http://cellreports.cell.com/ Cell Reports,23 August 2012; 10.1016/j.celrep.2012.07.015

The article notes that: ‘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:  H19and 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.’

Chas Easley and Jerry Schatten write that:‘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.’

 - Gerald Schatten, Ph.D.

Director, Pittsburgh Development Center Deputy Director, Magee-Women's Research Institute Professor & Vice-Chair of Obstetrics, Gynecology & Reproductive Sciences; Professor of Cell Biology & Physiology, & of Bioengineering; Director, Division of Developmental & Regenerative Medicine; University of Pittsburgh  School of Medicine


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