Recapitulating egg and sperm development in the dish for the first time

Amazing stuff!

"... For the first time, they were able to get these cells to start the complex process of meiosis – which is key to creating eggs and sperm – outside the human body.

This breakthrough, published in Science Advances, could one day lead to treatments to fight infertility. ...

However, replicating meiosis outside the human body, which could eventually allow fertility specialists to create healthy gametes for disadvantaged parents, has been extremely challenging.

Now, researchers ... have developed an in vitro method that enables the differentiation of induced pluripotent stem cells (iPSCs) along the path of meiosis. By introducing a cocktail of genes into iPSCs that turn on meiosis-specific gene expression programs, as well as drugs that alter the processing of signals in cells, the team is the first to observe live human cells initiating meiosis outside of the body. ..."

From the abstract:

"Meiotic failure is a major cause of infertility, but the lack of an in vitro model of human meiosis is a barrier to understanding its mechanism.

Here, we establish a method to initiate meiosis directly from male or female human-induced pluripotent stem cells (iPSCs).

DNMT1 inhibition, retinoid signaling activation, and overexpression of regulatory factors (antiapoptotic BCL2 and promeiotic HOXB5, BOLL, or MEIOC) rapidly activates meiosis over a 15-day protocol.

Our protocol bypasses the primordial germ cell stage and directly generates cells expressing genes similar to meiotic oogonia, including oogonia markers, all synaptonemal complex components, and meiotic recombination machinery. DNMT1 inhibition rapidly erases DNA methylation, including at imprinting control regions and promoters of meiotic genes.

Microscopy shows key aspects of meiosis, including chromosome axis formation and synapsis in live human cells. Our model of human meiosis provides opportunities for studying this critical reproductive process under chemically defined conditions in vitro."

Recapitulating egg and sperm development in the dish "New stem cell differentiation method is first to induce meiosis, a critical step in egg and sperm cell development, with potential for drug development and future fertility treatments"

Initiation of meiosis from human iPSCs under defined conditions through identification of regulatory factors (open access)

Fig. 4. Time course scRNA-seq analysis of meiosis induction.