PSCDGs of mouse multipotent adult germline stem cells can enter and progress through meiosis to form haploid male germ cells in vitro

Spermatogonial stem cells (SSCs) provide the basis for spermatogenesis throughout adult life by undergoing self-renewal and differentiation into sperm. SSC-derived cell lines called multipotent adult germline stem cells (maGSCs) were recently shown to be pluripotent and to have the same potential as embryonic stem cells (ESCs). In a differentiation protocol using retinoic acid (RA) and based on a double selection strategy, we have shown that ESCs are able to undergo meiosis and produce haploid male germ cells in vitro. Using this differentiation protocol we have now succeeded to generate haploid male germ cells from maGSCs in vitro. maGSCs derived from a Stra8-EGFP transgenic mouse line wer…

PAR-2 depletion protects against the development of pulmonary hypertension

In Vitro-Differentiated Embryonic Stem Cells Give Rise to Male Gametes that Can Generate Offspring Mice

SummaryMale gametes originate from a small population of spermatogonial stem cells (SSCs). These cells are believed to divide infinitely and to support spermatogenesis throughout life in the male. Here, we developed a strategy for the establishment of SSC lines from embryonic stem (ES) cells. These cells are able to undergo meiosis, are able to generate haploid male gametes in vitro, and are functional, as shown by fertilization after intracytoplasmic injection into mouse oocytes. Resulting two-cell embryos were transferred into oviducts, and live mice were born. Six of seven animals developed to adult mice. This is a clear indication that male gametes derived in vitro from ES cells by this…

Männliche Keimzellen aus embryonalen Stammzellen

Zusammenfassung Die Grundlage für die lebenslange Differenzierung männlicher Keimzellen sind die spermatogonialen Stammzellen (SSC) im Testis (etwa 0,03% aller Testiszellen). Es ist gelungen, aus embryonalen Stammzellen (ES-Zellen) der Maus SSC zu generieren, die die Meiose und die Haploidisierung durchlaufen. Werden die entstehenden Spermien mit Hilfe von ICSI in unbefruchtete Eizellen eingebracht und die entstandenen 2-Zeller in den Uterus pseudoschwangerer Mäuse transferiert, werden lebensfähige Mäuse geboren. Die von uns entwickelte Strategie ermöglicht molekulare und biochemische Untersuchungen zur männlichen Keimzelldifferenzierung, insbesondere auch zur Meiose und zur Haploidisierung.