Interspecies Chimerism with Mammalian Pluripotent Stem Cells.
Interspecies Chimerism with Mammalian Pluripotent Stem Cells.
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DOI：
10.1016/j.cell.2016.12.036
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发表时间：
2017-01-26
期刊：
影响因子：
64.5
通讯作者：
Izpisua Belmonte JC
中科院分区：
文献类型：
--
作者：
Wu J;Platero-Luengo A;Sakurai M;Sugawara A;Gil MA;Yamauchi T;Suzuki K;Bogliotti YS;Cuello C;Morales Valencia M;Okumura D;Luo J;Vilariño M;Parrilla I;Soto DA;Martinez CA;Hishida T;Sánchez-Bautista S;Martinez-Martinez ML;Wang H;Nohalez A;Aizawa E;Martinez-Redondo P;Ocampo A;Reddy P;Roca J;Maga EA;Esteban CR;Berggren WT;Nuñez Delicado E;Lajara J;Guillen I;Guillen P;Campistol JM;Martinez EA;Ross PJ;Izpisua Belmonte JC
种间胚泡互补使异种多能干细胞（PSC）衍生物的器官特异性富集成为可能。在此，我们建立了基于crispr - cas9介导的合子基因组编辑的多功能囊胚互补平台，并在基因编辑的器官发生残疾小鼠的几种组织中显示了大鼠psc衍生物的富集。除了深入了解物种进化、胚胎发生和人类疾病之外，种间囊胚互补可能使器官大小、解剖学和生理学更接近人类的动物产生人类器官。然而，迄今为止，人类psscs是否能够促进非啮齿动物物种的嵌合体形成仍然未知。我们系统地评估了几种类型的人造血干细胞嵌合能力，使用更多样化的哺乳动物分支，有蹄类。我们发现naïve高效能干细胞在猪和牛的着床前囊胚中都有良好的植入，但对着床后的猪胚胎的贡献有限。相反，中间型hPSC表现出更高程度的嵌合，能够在植入后的猪胚胎中产生分化的后代。人多能干细胞在牛和猪的胚胎着床前均可植入，但在猪胚胎着床后嵌合作用有限。
Interspecies blastocyst complementation enables organ-specific enrichment of xenogenic pluripotent stem cell (PSC) derivatives. Here, we establish a versatile blastocyst complementation platform based on CRISPR-Cas9-mediated zygote genome editing and show enrichment of rat PSC-derivatives in several tissues of gene-edited organogenesis-disabled mice. Besides gaining insights into species evolution, embryogenesis, and human disease, interspecies blastocyst complementation might allow human organ generation in animals whose organ size, anatomy, and physiology are closer to humans. To date, however, whether human PSCs (hPSCs) can contribute to chimera formation in non-rodent species remains unknown. We systematically evaluate the chimeric competency of several types of hPSCs using a more diversified clade of mammals, the ungulates. We find that naïve hPSCs robustly engraft in both pig and cattle pre-implantation blastocysts but show limited contribution to post-implantation pig embryos. Instead, an intermediate hPSC type exhibits higher degree of chimerism and is able to generate differentiated progenies in post-implantation pig embryos. Human pluripotent stem cells robustly engraft into both cattle and pig pre-implantation blastocysts, but show limited chimeric contribution to post-implantation pig embryos.
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