Generation of Functional Organs Using a Cell-Competitive Niche in Intra- and Inter-species Rodent Chimeras.

Generation of Functional Organs Using a Cell-Competitive Niche in Intra- and Inter-species Rodent Chimeras.
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DOI:
10.1016/j.stem.2020.11.019
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发表时间:
2021-01-07
期刊:
影响因子:
23.9
通讯作者:
Nakauchi H
Nakauchi H
中科院分区:
医学1区
文献类型:
--
作者:
Nishimura T;Suchy FP;Bhadury J;Igarashi KJ;Charlesworth CT;Nakauchi H

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Interspecies organ generation via blastocyst complementation has succeeded in rodents, but not yet in evolutionally more distant species: Early developmental arrest hinders formation of highly chimeric fetuses. We demonstrate that deletion of Insulin-like growth factor 1 receptor (Igf1r) in mouse embryos creates a permissive “cell competitive niche”, in several organs significantly augmenting both mouse intra- and mouse/rat interspecies donor chimerism that continuously increases from embryonic day 11 onward, sometimes even taking over entire organs within intra-species chimeras. Since Igf1r deletion allows evasion of early developmental arrest, inter-species fetuses with high levels of organ chimerism can be generated via blastocyst complementation. This observation should facilitate donor cell contribution to host tissues, resulting in whole-organ generation via blastocyst complementation across wide evolutionary distances.
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