Generating functional cells through enhanced interspecies chimerism with human pluripotent stem cells.

ABSTRACT: Obtaining functional human cells through interspecies chimerism with human pluripotent stem cells (hPSCs) remains unsuccessful due to its extremely low efficiency. Here, we show that hPSCs failed to differentiate and contribute teratoma in the presence of mouse PSCs (mPSCs), while MYCN, a pro-growth factor, dramatically promotes hPSC contributions in teratoma co-formation by hPSCs/mPSCs. MYCN combined with BCL2 (M/B) greatly enhanced conventional hPSCs to integrate into pre-implantation embryos of different species, such as mice, rabbits, and pigs, and substantially contributed to mouse post-implantation chimera in embryonic and extra-embryonic tissues. Strikingly, M/B-hPSCs injected into pre-implantation Flk-1^+/- mouse embryos show further enhanced chimerism that allows for obt

SUBMITTER: Zhu Y 

PROVIDER: S-EPMC9133581 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature