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首页> 美国卫生研究院文献>NPJ Regenerative Medicine >Running the full human developmental clock in interspecies chimeras using alternative human stem cells with expanded embryonic potential
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Running the full human developmental clock in interspecies chimeras using alternative human stem cells with expanded embryonic potential

机译：使用具有扩大胚胎潜力的替代人干细胞在嵌合嵌合体中运行全人发育时钟

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Top: Murine ESC (mESC; red) are derived from pre-implantation morula- or blastocyst-staged murine embryos, and capture a naïve epiblast-like pluripotent state. mESCs can differentiate into all three germ-layers via in vitro directed differentiation, in vivo teratomas, and in vivo morula/blastocyst chimera assays. The murine pluripotent state can also be obtained through epigenetic reprogramming of somatic cells with ectopic expression of Yamanaka factors. Murine extended potential stem cells (mEPSCs; green) possess both embryonic and extra-embryonic differentiation potency and can be derived via chemical reprogramming of cleavage-stage murine blastomere cells of mESCs. Stem cells resembling the molecular phenotype of 2-cell (2C) cleavage-staged blastomeres (purple) putatively possessing totipotent-like molecular characteristics can be isolated from mESC cell cultures122, or through the inductive expression of key totipotent factors (e.g., Dux and NELF-A). Bottom: Although conventional hESC (blue) are similarly derived from the pre-implantation stages of IVF-derived morula or blastocyst-staged human embryos, they are phenotypically similar in culture with post-implantation primed murine epiblast stem cells (mEpiSC; blue). A primed, mEpiSC-like state of pluripotency is also attained through the epigenetic reprogramming of human somatic cells by Yamanaka factors into hiPSC. Multiple methods for reverting conventional hPSC to naïve human pluripotent stem cells (N-hPSC; red) with mESC-like pluripotency have been reported employing various small molecule inhibitor cocktails or via transgene expression of key factors10. Self-renewing human totipotent stem cells (purple) with phenotypic equivalence to four to eight-cell or cleavage stage human blastomeres have not yet been described.
机译：TOP：鼠主义（MESC; RED）衍生自预注入的森林或胚泡分段的鼠胚胎，并捕获幼稚状不同的多能状态。 MESCS可以通过体外定向分化，体内畸胎瘤和体内莫拉/胚泡嵌合体测定分化为所有三种种系。鼠多能状态也可以通过具有山尾表的异位表达的体细胞的表观遗传重编程来获得。鼠长潜在干细胞（MEPSCs;绿色）具有胚胎和胚胎分化效力，可以通过麦塞斯的裂解阶段小鼠斑节细胞的化学重编程来源。具有2细胞（2C）裂解分段（紫色）的分子表型的干细胞可以从MESC细胞培养物122中分离出特异性的分子特征，或通过关键无阻素因素的感应表达（例如，Dux和Nelf -一种）。底部：虽然常规HESC（蓝色）类似地衍生自IVF衍生的森拉或胚泡术术人胚胎的预植入阶段，但它们在具有植入后灌注鼠外血管干细胞（MPESC;蓝色）的培养方面是相似的。通过山卡钟因子将人体细胞的表观重新编程为HIPSC，还获得了一种底漆的蜂鸣的多能性的多能性状态。据报道，将常规HPSC重新调解常规HPSC的方法与麦克斯皮多能性的多能性多能干细胞（N-HPSC;红色）采用各种小分子抑制剂鸡尾酒或通过转基因表达的关键因子10的转基因表达。尚尚未描述自我更新人类彻底转化干细胞（紫色），其具有表型当量至四个细胞或裂解阶段的人脱裂剂。

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