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Interspecies Chimerism with Mammalian Pluripotent Stem Cells
- Source :
- Cell, vol 168, iss 3
- Publication Year :
- 2017
- Publisher :
- eScholarship, University of California, 2017.
-
Abstract
- Interspecies blastocyst complementation enables organ-specific enrichment of xenogenic pluripotent stem cell (PSC) derivatives. Here, we establish a versatile blastocyst complementation platform based on CRISPR-Cas9-mediated zygote genome editing and show enrichment of rat PSC-derivatives in several tissues of gene-edited organogenesis-disabled mice. Besides gaining insights into species evolution, embryogenesis, and human disease, interspecies blastocyst complementation might allow human organ generation in animals whose organ size, anatomy, and physiology are closer to humans. To date, however, whether human PSCs (hPSCs) can contribute to chimera formation in non-rodent species remains unknown. We systematically evaluate the chimeric competency of several types of hPSCs using a more diversified clade of mammals, the ungulates. We find that naive hPSCs robustly engraft in both pig and cattle pre-implantation blastocysts but show limited contribution to post-implantation pig embryos. Instead, an intermediate hPSC type exhibits higher degree of chimerism and is able to generate differentiated progenies in post-implantation pig embryos.
- Subjects :
- 0301 basic medicine
Male
Sus scrofa
Inbred C57BL
Regenerative Medicine
Medical and Health Sciences
Rats, Sprague-Dawley
Mice
Genome editing
CRISPR
Induced pluripotent stem cell
Genetics
Mammals
Gene Editing
Pediatric
Mice, Inbred ICR
Zygote
Stem Cell Research - Induced Pluripotent Stem Cell - Human
Embryo
Biological Sciences
Inbred ICR
Complementation
medicine.anatomical_structure
human naïve pluripotent stem cells
human-pig chimeric embryo
Female
CRISPR-Cas9
Biotechnology
Pluripotent Stem Cells
Biology
Chimerism
General Biochemistry, Genetics and Molecular Biology
Article
03 medical and health sciences
Chimera (genetics)
zygote genome editing
medicine
Animals
Humans
organ and tissue generation
Blastocyst
Stem Cell Research - Embryonic - Human
interspecies chimera
Stem Cell Research - Induced Pluripotent Stem Cell
Mammalian
human-cattle chimeric embryo
Embryo, Mammalian
Stem Cell Research
Rats
Mice, Inbred C57BL
030104 developmental biology
Cattle
Sprague-Dawley
Generic health relevance
CRISPR-Cas Systems
interspecies blastocyst complementation
Developmental Biology
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Cell, vol 168, iss 3
- Accession number :
- edsair.doi.dedup.....7260a1f6dad23dde10b5ef15698f08b5