近日，日本东京大学Hiromitsu Nakauchi及其团队发现，通过改变细胞竞争微环境可在嵌合体中产生功能性器官。相关论文于2020年12月28日在线发表于国际学术期刊《细胞—干细胞》。

研究人员证明删除小鼠胚胎中的胰岛素样生长因子1受体（Igf1r）能够在多个器官中创造一个“细胞竞争性微环境”，从而大大增加了小鼠种内和小鼠/大鼠种间供体的嵌合体，这种嵌合体从胚胎第11天开始就不断增加，有时甚至占据种内嵌合体的整个器官。由于Igf1r缺失可以避免早期的发育停滞，因此可以通过囊胚互补产生具有高水平器官嵌合体的种间胚胎。该观察结果能够促进供体细胞对宿主组织的贡献，从而通过跨越进化距离的囊胚互补产生完整器官。

据悉，通过囊胚互补的种间器官产生在啮齿动物中已经成功，但是在进化上更遥远的物种中还没有成功。早期发育停滞阻碍了高度嵌合胎儿的形成。

附：英文原文

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

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

Issue&Volume: 2020-12-28

Abstract: Interspecies organ generation via blastocyst complementation has succeeded in rodents,but not yet in evolutionally more distant species. Early developmental arrest hindersthe formation of highly chimeric fetuses. We demonstrate that the deletion of insulin-likegrowth 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 donorchimerism that continuously increases from embryonic day 11 onward, sometimes eventaking over entire organs within intraspecies chimeras. Since Igf1r deletion allows the evasion of early developmental arrest, interspecies fetuses withhigh levels of organ chimerism can be generated via blastocyst complementation. Thisobservation should facilitate donor cell contribution to host tissues, resulting inwhole-organ generation via blastocyst complementation across wide evolutionary distances.

DOI: 10.1016/j.stem.2020.11.019

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30583-X