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Transfecting and Nucleofecting Human Induced Pluripotent Stem Cells
Published on: October 5, 2011
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BMI1 enables interspecies chimerism with human pluripotent stem cells
Ke Huang1,2,3,4, Yanling Zhu1,2,3,4,5, Yanlin Ma6
1Key Laboratory of Regenerative Biology of Chinese Academy of Sciences, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, 510530, Guangzhou, China.
Nature Communications
|November 9, 2018
Summary
Forced expression of BMI1 in human pluripotent stem cells (hPSCs) prevents apoptosis, enabling their integration into early embryos and improving interspecies chimera formation across species.
Area of Science:
- Developmental Biology
- Stem Cell Biology
- Reproductive Biology
Background:
- Human pluripotent stem cells (hPSCs) show limited contribution to interspecies chimeras.
- This limitation may stem from their primed state, hindering integration into pre-implantation embryos.
Purpose of the Study:
- To investigate the barriers to hPSC contribution in interspecies chimeras.
- To identify strategies for enhancing hPSC integration and chimera formation.
Main Methods:
- Injected conventional hPSCs and BMI1-overexpressing hPSCs into mouse pre-implantation embryos.
- Assessed hPSC survival, integration, and contribution to embryonic and extra-embryonic tissues.
- Tested BMI1's effect in rabbit and pig embryos.
Main Results:
- Conventional hPSCs underwent rapid apoptosis upon injection into mouse embryos.
- Forced BMI1 expression in hPSCs overcame apoptosis, enabling integration and chimera contribution.
- BMI1 facilitated hPSC integration into rabbit and pig embryos.
- High BMI1 expression and anti-apoptosis correlated with naïve hPSCs forming mouse chimeras.
Conclusions:
- Apoptosis is a primary barrier to hPSC-based interspecies chimerism.
- BMI1 overexpression is a viable strategy to enhance hPSC integration and chimera formation.
- Findings provide a rationale for improving interspecies chimera generation using hPSCs.
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