To us, this was both unexpected and very interesting.

In our case, we successfully obtained embryo-like structures; however, although the cells were reprogrammed to an earlier developmental stage, they did not appear to generate precursors. Instead, they transitioned directly into the various early embryonic fates.

Thank you for the comment and question. We think that if we can reprogram cells into precursors of all embryonic lineages, they should then be able to self-organize into an embryo model.

(8/8) Our v1.0, limitations remain (see Limitations section), but we hope, alongside other models, it can help advance human embryogenesis research.

Visit the lab website for free access to our study (under publications section)

(7/8) There’s more inside: signaling landscapes, PGCs, primary-to-secondary yolk sac transition…

(6/8) The molecular signatures show strong alignment and high identity scores with human embryo references.

(5/8) ….And they keep going, entering gastrulation!

(4/8) If these cells can generate all early fates, then they should be able to do so in a self-organized manner, forming embryo-like structures……. and they did! (All we had to do was sit back and let the cells do their work.)

(3/8) The results went beyond expectations: alongside naïve epi, TE & hypoblast, we also saw extraembryonic mesoderm emerge 🤯

(2/8) From our work in the mouse system we hypothesised that STAT3 could reprogram human cells from a post- to a pre-implantation fate, but the breakthrough came only after we also added TGFβ inhibition.

(3/3) Fast forward ⏩ @cc0447.bsky.social Jinyi Wu et al. investigated this in human cells. Curious to see what they pulled off? Stay tuned!

(2/3) … this was actually a side finding in that study🙃

www.cell.com/cell-stem-ce...

However, we thought this could be paralleling early embryo development and have since been exploring it to generate embryo models.

I believe they will, but we’re not there yet.

😀

Thank you so much Alex!

A big thanks to all authors, especially Professor Naihe Jing and Penglei Shen for guiding our embryo model into organogenesis, and to our PhD students Jiahui Huang and Wei Guan for their efforts. And of course, to Huanhuan Li, the driving force behind this work.( 3/3)

Starting from PSCs, a brief reprogramming step gives rise to “embryo founder-like cells” (EFCs). EFCs segregate embryonic and extraembryonic lineages and self-organize to closely mirror natural embryo development, both morphologically and at the molecular level.
authors.elsevier.com/sd/article/S...