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BMI1 enables interspecies chimerism with human pluripotent stem cells
- Source :
- Nature Communications, Vol 9, Iss 1, Pp 1-11 (2018), Nature Communications
- Publication Year :
- 2018
- Publisher :
- Nature Publishing Group, 2018.
-
Abstract
- 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.<br />Conventional human pluripotent stem cells (hPSCs) fail to contribute to interspecies chimaeras when injected into mouse blastocysts. Here the authors show that forced expression of BMI1 overcomes apoptosis of hPSCs in blastocysts of mouse, rabbit and pig allowing them to contribute to chimaeras.
- Subjects :
- 0301 basic medicine
Pluripotent Stem Cells
Swine
Science
Extraembryonic Membranes
General Physics and Astronomy
Apoptosis
Cell lineage
macromolecular substances
Biology
Chimerism
General Biochemistry, Genetics and Molecular Biology
Article
03 medical and health sciences
Chimera (genetics)
Species Specificity
Animals
Humans
Cell Lineage
Induced pluripotent stem cell
lcsh:Science
reproductive and urinary physiology
Polycomb Repressive Complex 1
Mice, Inbred ICR
Multidisciplinary
Embryo
General Chemistry
Embryonic stem cell
Cell biology
030104 developmental biology
Blastocyst
BMI1
embryonic structures
lcsh:Q
Rabbits
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 9
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....310d2c64f0f80ca1a97a649baf2831cf