BMI1 enables interspecies chimerism with human pluripotent stem cells.
Ke HuangYanling ZhuYanlin MaBentian ZhaoNana FanYuhang LiHong SongShilong ChuZhen OuyangQuanjun ZhangQi XingChengdan LaiNan LiTian ZhangJiaming GuBaoqiang KangYongli ShanKeyu LaiWenhao HuangYuchan MaiQing WangJinbing LiAiping LinYanqi ZhangXiaofen ZhongBaojian LiaoLiangxue LaiJie-Kai ChenDuanqing PeiGuangjin PanPublished in: Nature communications (2018)
Human pluripotent stem cells (hPSCs) exhibit very limited contribution to interspecies chimeras. One explanation is that the conventional hPSCs are in a primed state and so unable to form chimeras in pre-implantation embryos. Here, we show that the conventional hPSCs undergo rapid apoptosis when injected into mouse pre-implantation embryos. While, forced-expression of BMI1, a polycomb factor in hPSCs overcomes the apoptosis and enables hPSCs to integrate into mouse pre-implantation embryos and subsequently contribute to chimeras with both embryonic and extra-embryonic tissues. In addition, BMI1 also enables hPSCs to integrate into pre-implantation embryos of other species, such as rabbit and pig. Notably, BMI1 high expression and anti-apoptosis are also indicators for naïve hPSCs to form chimera in mouse embryos. Together, our findings reveal that the apoptosis is an initial barrier in interspecies chimerism using hPSCs and provide a rational to improve it.
Keyphrases
- pluripotent stem cells
- endoplasmic reticulum stress
- oxidative stress
- cell cycle arrest
- body mass index
- cell death
- endothelial cells
- poor prognosis
- weight gain
- allogeneic hematopoietic stem cell transplantation
- gene expression
- pi k akt
- binding protein
- genome wide
- cell proliferation
- acute myeloid leukemia
- weight loss
- genetic diversity
- sensitive detection