Details

Autor(en) / Beteiligte

• Nishimura, Toshiya
• Suchy, Fabian P.
• Bhadury, Joydeep
• Igarashi, Kyomi J.
• Charlesworth, Carsten T.
• Nakauchi, Hiromitsu

Titel

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

Ist Teil von

• Cell stem cell, 2021-01, Vol.28 (1), p.141-149.e3

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• Interspecies organ generation via blastocyst complementation has succeeded in rodents, but not yet in evolutionally more distant species. Early developmental arrest hinders the formation of highly chimeric fetuses. We demonstrate that the 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 intraspecies and mouse/rat interspecies donor chimerism that continuously increases from embryonic day 11 onward, sometimes even taking over entire organs within intraspecies chimeras. Since Igf1r deletion allows the evasion of early developmental arrest, interspecies 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. [Display omitted] •Igf1r null mouse embryos provide an open niche that augments donor chimerism•Donor chimerism increases from mid- to late developmental stages in this niche•Enhanced donor chimerism results in some entire donor-derived organs in chimeras•This niche augments donor chimerism in interspecies chimeras. Nishimura et al. demonstrate that Igf1r deletion in mouse embryos creates a “cell-competitive niche,” in several organs, significantly augmenting both intra- and interspecies donor chimerism. In this permissive niche, donor chimerism gradually increases from embryonic day 11 onward without affecting early embryo development, sometimes even taking over entire organs.