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

Cell Stem Cell. 2021 Jan 7;28(1):141-149.e3. doi: 10.1016/j.stem.2020.11.019. Epub 2020 Dec 28.


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.

Keywords: blastocyst complementation; cell competition; chimera; embryonic stem cell; induced pluripotent stem cell; interspecies chimera; niche; organ generation; pluripotent stem cell; stem cell.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Blastocyst
  • Chimera*
  • Chimerism
  • Mice
  • Pluripotent Stem Cells*
  • Rats
  • Rodentia