A step toward lab‑grown sperm: Scientists turn stem cells into early sperm cells in a mini‑testis

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"... In a recent study published in Cell Stem Cell, scientists presented a recipe for transforming human blood-derived cells into immature primate sperm precursor cells in a mini-testis-like environment.

The researchers started with induced pluripotent stem cells (iPSCs) from humans and rhesus macaques, which are blank-slate cells that can be programmed to become almost any cell type. By exposing them to specific chemical signals, the researchers transformed them into primordial germ cell-like cells (PGCLCs), which are lab-grown versions of the earliest embryonic cells that eventually develop into germline cells, in this case sperm cells. ..."

From the highlights and abstract:

"Highlights

• Human and macaque iPSCs generate spermatogonia after testis reconstitution

• Induced germ cells form xenogeneic reconstituted testes with mouse somatic cells

• Differentiated germ cells recapitulate in vivo phenotypes and transcriptomes

• iPSC-derived spermatogonia express prepachytene piRNAs

Summary

Failures in germline development drive male infertility, but the lack of model systems that recapitulate human spermatogenesis hampers therapeutic development.

Here, we develop a system to differentiate human-induced pluripotent stem cells (iPSCs) into primordial germ cell-like cells that self-organize with mouse fetal testicular cells into seminiferous tubule-like structures within a xenogeneic reconstituted testis (xrTestis).

Subsequent transplantation of xrTestes into immunodeficient mice results in efficient generation of male germ cells up to meiotic onset, including spermatogonia with evidence of prepachytene PIWI-interacting RNA (piRNA) biogenesis, as well as differentiating spermatogonia and rare preleptotene spermatocytes exhibiting transcriptomic and phenotypic similarities to their in vivo counterparts.

As future clinical applications will require testing in non-human primates, we apply a similar strategy to differentiate rhesus iPSCs through fetal germ cell stages into spermatogonia and differentiating spermatogonia.

Together, these platforms provide a foundation for studying primate germ cell lineages and represent a step toward in vitro gametogenesis."

A step toward lab‑grown sperm: Scientists turn stem cells into early sperm cells in a mini‑testis

Generation of spermatogonia from human and non-human primate pluripotent stem cells (open access)

Graphical abstract