nature

当前位置: Nature » 细胞生物学 » 正文

Cell Res:中科院动物所胡宝洋研究组利用人胚胎干细胞产生异种嵌合体

摘要 : 2017年11月3日,国际学术权威刊物自然出版集团旗下子刊《Cell Research》杂志在线发表了中国科学院动物研究所胡宝洋、李伟、周琪研究组合作的一篇研究论文,研究组利用人胚胎干细胞产生异种嵌合体。

2017年11月3日,国际学术权威刊物自然出版集团旗下子刊《Cell Research》杂志在线发表了中国科学院动物研究所胡宝洋、李伟、周琪研究组合作的一篇研究论文,研究组利用人胚胎干细胞产生异种嵌合体。研究成果题为Human embryonic stem cells contribute to embryonic and extraembryonic lineages in mouse embryos through inhibition of apoptosis。

干细胞具有多潜能的分化能力,能够在体内、体外分化成不同类型的细胞、组织甚至器官。通过干细胞的异种嵌合技术在猪等大动物体内实现异种再造器官,将为器官移植中供体器官严重短缺提供新方法。然而,人类胚胎干细胞在异种体内分化潜能尚不完全清楚,细胞存活、分化识别、发育时程等关键问题仍未解决,依然存在严重的技术壁垒。

研究组通过在Primed状态人类胚胎干细胞中过表达抗凋亡基因BCL2及BCL2L1,并在小鼠四细胞发育时期进行胚胎注射,获得了Primed状态人胚胎干细胞嵌合的人-鼠异种嵌合小鼠胚胎,并证明其同时具有胚内、胚外组织的嵌合能力。此项工作将为开展人类胚胎干细胞异种嵌合研究,并最终获得能够移植的人类器官提供新的方法和思路。

研究首先将Primed状态的人类胚胎干细胞过表达BCL2、BCL2L1两个抗凋亡基因,并将其注射到四细胞期的小鼠早期胚胎中。研究发现,过表达BCL2、BCL2L1基因的人胚胎干细胞在小鼠胚胎中的细胞凋亡水平显著降低,显著提高其在小鼠早期胚胎中的贡献比例。进一步研究揭示,人胚胎干细胞在小鼠体内具有三胚层的分化能力,在嵌合体发育的E10.5天分化还可成为功能细胞,且人干细胞的嵌合比例可高达1%。

值得注意的是,该研究在异种嵌合囊胚的滋养外胚层细胞(TE)及后续分化的胚外组织中检测到人胚胎干细胞的贡献,证明Primed状态人胚胎干细胞具有向胚外组织发育的能力。上述研究通过提高Primed状态人胚胎干细胞的抗凋亡能力证明其具有异种嵌合的能力,这为利用人胚胎干细胞制备异种嵌合体的研究提供新思路,也为进一步研究人类胚胎干细胞多能性状态的调控机制提供了指导。

人胚胎干细胞产生异种嵌合体

原文链接:

Human embryonic stem cells contribute to embryonic and extraembryonic lineages in mouse embryos upon inhibition of apoptosis

原文摘要:

Recently, interspecies chimera formation has been established in rodents by injection of rat pluripotent stem cells (PSCs) into mouse early embryos, and such a system provides an in vivo assay to test the developmental potential of human PSCs (hPSCs)1. In addition, the interspecies chimeras formed between hPSCs and large animal embryos would open new avenues to generate human tissues and organs for regenerative medicine2. In rodents, embryonic stem cells (ESCs) and epiblast stem cells (EpiSCs) have been derived from inner cell mass (ICM) of the blastocyst and post-implantation epiblast respectively3,4. Although both being pluripotent, the ESCs and EpiSCs are considered to represent two distinct states of pluripotency, the naïve and primed pluripotent state. only naïve state ESCs can colonize the early embryos before the blastocyst stage to form adult chimeras and transmit to the germline, while the primed state EpiSCs can only integrate into the post-implantation embryos5,6. Intriguingly, although derived from the ICM, the human ESCs (hESCs) are similar to the mouse EpiSCs in many aspects such as the morphology and self-renewal pathways, hence they are considered to represent the primed pluripotent state. Several studies have reported the generation of human-animal interspecies chimeras using the stage-matching hESCs. For example, primed hPSCs were engrafted into in vitro cultured gastrula-stage mouse embryos to form chimeras, and the primed hPSCs were also converted into a naïve-like state and then were injected into pre-implantation embryos to form mouse or pig chimeras7,8,9. Recently, a non-stage-matching approach has been established to generate mouse-rat interspecies chimeras by inhibiting apoptosis of the primed ESCs10. We hence hypothesize that inhibition of apoptosis may enable the primed hESCs to form interspecies chimeras upon injection into mouse pre-implantation stage embryos.

来源: Cell Research 浏览次数:0

热门文章TOP

RSS订阅 - 填写您的邮件地址,订阅我们的精彩内容: - 网站地图
网站联系电话:020-87540820 备案号:粤ICP备11050685号-8 增值电信业务经营许可证:粤B2-20120479
©2011-2015 生物帮 All rights reserved.