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首页 » 干细胞&iPS » PNAS:科学家鉴一过渡干细胞——骨形成蛋白干细胞

PNAS:科学家鉴一过渡干细胞——骨形成蛋白干细胞

来源:生物谷 2015-04-20 11:50

2015年4月20日 讯 /生物谷BIOON/ --先兆子痫是一种影响5%-8%的美国孕妇的疾病,该疾病引发的并发症通常会导致女性怀孕早期紧急剖腹产,这样才能挽救婴儿和母亲的生命,而科学家们认为先兆子痫是由一系列因素所引发的,包括浅胎盘等,浅胎盘和婴儿母源性血管不足直接相关。近日一篇发表在国际杂志PNAS上的研究论文中,来自密苏里大学的研究者通过研究成功培育生长了胎盘细胞,其可以帮助更好地进行先兆子痫发病机制的研究。

研究者Michael Roberts表示,胎盘细胞是一种未知形式的人类胚胎干细胞,这种新型干细胞可以帮助研究先兆子痫的发病机制及人类生育过程的其它过程。研究者将这种干细胞称之为骨形成蛋白干细胞,相比正常的胚胎干细胞而言其非常强劲而且容易对其进行操作;骨形成蛋白干细胞是一种介于胚胎干细胞和最后发育形成后的细胞间的一种过渡状态的细胞,研究者可以利用这种干细胞来理解胚胎的形成过程以及进行诸如先兆子痫等出生前疾病发病机制的研究。

胚胎干细胞具有多能性,这就意味着研究者可以利用其分化形成一系列不同的细胞,比如肌肉细胞、骨细胞等,这项研究中研究者想利用短期添加骨形成蛋白-4使胚胎干细胞分化生长为胚胎细胞,同时研究者还添加了两种药物,其可以暂时抑制干细胞多能状态的关键生化反应。

如果不形成胎盘细胞,干细胞就会生长成为以前的一种未被观察的状态,也就是研究者所谓的骨形成蛋白干细胞,相比传统干细胞而言这种干细胞很容易在实验室进行操作,而且容易生长,具有较强的均一性,这就意味着培养中的细胞都会表现出一致的遗传信息。

研究者Roberts表示,此前传统观念认为胚胎干细胞的过渡会径直从干细胞到最终的分化细胞,而本文中新型干细胞的发现则可以帮助研究者认识到胚胎干细胞是以许多不同过渡阶段的细胞而存在的,相关研究就可以帮助研究人员未来进行更加有效的干细胞研究以及开发治疗婴儿出生前相关疾病的新型靶向疗法。 (生物谷Bioon.com)

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Heightened potency of human pluripotent stem cell lines created by transient BMP4 exposure.

Ying Yang, Katsuyuki Adachi, Megan A. Sheridan, Andrei P. Alexenko, Danny J. Schust, Laura C. Schulz, Toshihiko Ezashi, R. Michael Roberts.

Human pluripotent stem cells (PSCs) show epiblast-type pluripotency that is maintained with ACTIVIN/FGF2 signaling. Here, we report the acquisition of a unique stem cell phenotype by both human ES cells (hESCs) and induced pluripotent stem cells (iPSCs) in response to transient (24–36 h) exposure to bone morphogenetic protein 4 (BMP4) plus inhibitors of ACTIVIN signaling (A83-01) and FGF2 (PD173074), followed by trypsin dissociation and recovery of colonies capable of growing on a gelatin substratum in standard medium for human PSCs at low but not high FGF2 concentrations. The self-renewing cell lines stain weakly for CDX2 and strongly for NANOG, can be propagated clonally on either Matrigel or gelatin, and are morphologically distinct from human PSC progenitors on either substratum but still meet standard in vitro criteria for pluripotency. They form well-differentiated teratomas in immune-compromised mice that secrete human chorionic gonadotropin (hCG) into the host mouse and include small areas of trophoblast-like cells. The cells have a distinct transcriptome profile from the human PSCs from which they were derived (including higher expression of NANOG, LEFTY1, and LEFTY2). In nonconditioned medium lacking FGF2, the colonies spontaneously differentiated along multiple lineages, including trophoblast. They responded to PD173074 in the absence of both FGF2 and BMP4 by conversion to trophoblast, and especially syncytiotrophoblast, whereas an A83-01/PD173074 combination favored increased expression of HLA-G, a marker of extravillous trophoblast. Together, these data suggest that the cell lines exhibit totipotent potential and that BMP4 can prime human PSCs to a self-renewing alternative state permissive for trophoblast development. The results may have implications for regulation of lineage decisions in the early embryo.

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