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Interspecies Chimerism with Mammalian Pluripotent Stem Cells (CONCLUSION…
Interspecies Chimerism with Mammalian Pluripotent Stem Cells
HYPOTHESIS
"We systematically evaluate the chimeric competency of several types of human PSCs using a more diversified clade of mammals" pigs and cattle
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Chimerism/chimera- an organism containing a mixture of genetically different tissues, formed by processes such as fusion of early embryos, grafting, or mutation
So far studies show matching developmental timing is crutial for chimera formation when introducing PSCs into a developing embryo of the same species
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It is unclear whether naive PCSs can be used to generate chimeras between more distantly related species
All reported attempts on generating human PSC-derived interspecies chimeras have used the mouse as the host animal and the results obtained suggest that this process is inefficient
Pluripotent stem cells (PSC) are generally in one of two states
naive state
unbiased developmental potential
primed state
cells are poised for linear differentiation
Naive Rat PSCs contribute to Rat-Mouse chimera formation
the presence of gallbladders were observed in rat-mouse chimeras (rats lack gallbladders)
A versatile CRSPR-Cas9-Mediated interspecies blastocyst complementation system
for the pancreas, heart, eyes and several other organs chimerized organs were generated enriched with rat cells
Naive rodent PSCs do not contribute to chimera formation in pigs
Generation of naive, intermediate and primed hiPSCs
Chimeric contribution of hiPSCs to Pig and Cattle Blastocysts
Chimeric contribution of hiPSCs to Post-implantation Pig Embryo
CONCLUSION
confirms that live rat-mouse chimeras with extensive contribution from naive rat PSCs can be generated and live a full mouse life-span
The multiplexing capability of CRISPR-Cas9 could potentially be harnessed for multiple lineage complementation
interspecies chimera formation involving hPCSs is inefficient
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FAC-hiPSCs, a putative intermediate PSC type between naive and primed pluripotent states, displayed a higher level of chimerism in post-implantation pig embryos