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PLoS ONE:羊水细胞重编程为iPS细胞

2010/11/29 来源:每日科学
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由于羊水干细胞能够生成各种类型的体细胞,因而一直被干细胞研究者们寄予厚望。科学家们期待在某一天他们能够利用羊水干细胞治疗各种疾病。然而到目前为止,由于胚胎仍是羊水干细胞的主要来源,因而引发了众多的伦理学问题。 近日柏林马克斯.普朗克分子遗传学研究所的科学家们成功地将羊水细胞转化为

由于羊水干细胞能够生成各种类型的体细胞,因而一直被干细胞研究者们寄予厚望。科学家们期待在某一天他们能够利用羊水干细胞治疗各种疾病。然而到目前为止,由于胚胎仍是羊水干细胞的主要来源,因而引发了众多的伦理学问题。

近日柏林马克斯.普朗克分子遗传学研究所的科学家们成功地将羊水细胞转化为多能干细胞(iPS细胞)。这些由羊水衍生的iPS细胞几乎与胚胎干细胞没有区别。然而,它们却能“记住”它们的起源。研究结果在线发表在国际学术刊物《公共科学图书馆.综合》(PLoS ONE)上。

现在胚胎干细胞的特殊潜能也能被运用到多种“成熟”体细胞中(例如皮肤和毛发细胞)。通过重编程可将这些细胞转化为“诱导多能干细胞”(iPS细胞)。iPS细胞具有胚胎干细胞的特性,可生成各种类型的人体细胞(多潜能),并且能够无限增殖。

带有记忆的干细胞

科学家们证实羊水iPS能够形成各种不同的人体细胞类型。在细胞重编程过程中,各种调控干细胞发育的基因明显地打开或保持活跃。他们还同时发现诱导多能干细胞能够记住它们原来的细胞类型。这证实了当前其他的研究结果,即当进行自发性分化时从各种不同组织衍生的iPS细胞更倾向于跟随它们预先注定的发育路线。“我们还不确定这种供体细胞类型的记忆是否有可能影响医学治疗,或是体细胞衍生的iPS将会成为最适合的治疗细胞类型,”

马克斯.普朗克分子遗传研究所的Katharina Wolfrum谨慎地表示。

羊水细胞相对于其他的细胞类型有着多个优势。一方面,在产前检查中常规采集羊水细胞能够对疾病进行早期筛查。在大多数情况下,获得的细胞总是比实际需要的要多。此外,羊水混合物中包含着各种来自于胎儿的不同类型的细胞,包括干细胞样细胞。

“环境诱导的突变在遗传上更为稳定。这或许意味着相比于其他的细胞类型,对羊水细胞重编程更快速,更容易。羊水衍生的iPS细胞极有可能能够填补对胚胎干细胞的需要,”马克斯.普朗克研究所的ames Adjaye解释说:“此外,还可在小孩出生前对采集的羊水细胞进行细胞重编程,以备不时之需。同时还可能帮助检测出哪些药物会对婴儿产生影响,以及能够为其所耐受。在未来,患病新生儿就能够利用从自己身体上获得的细胞进行疾病治疗。”(生物谷Bioon.com)

生物谷推荐英文摘要:

PLoS ONE doi:10.1371/journal.pone.0013703

The LARGE Principle of Cellular Reprogramming: Lost, Acquired and Retained Gene Expression in Foreskin and Amniotic Fluid-Derived Human iPS Cells

Katharina Wolfrum1,2, Ying Wang1, Alessandro Prigione1, Karl Sperling3, Hans Lehrach1, James Adjaye1,4*

1 Molecular Embryology and Aging Group, Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany, 2 Institute of Chemistry and Biochemistry, Department of Biology, Chemistry, and Pharmacy, Freie Universit?t Berlin, Berlin, Germany, 3 Institute of Human Genetics, Charité - Universit?tsmedizin Berlin, Berlin, Germany, 4 Stem Cell Unit, Department of Anatomy, Medical College, King Saud University, Riyadh, Saudi Arabia

Human amniotic fluid cells (AFCs) are routinely obtained for prenatal diagnostics procedures. Recently, it has been illustrated that these cells may also serve as a valuable model system to study developmental processes and for application in regenerative therapies. Cellular reprogramming is a means of assigning greater value to primary AFCs by inducing self-renewal and pluripotency and, thus, bypassing senescence. Here, we report the generation and characterization of human amniotic fluid-derived induced pluripotent stem cells (AFiPSCs) and demonstrate their ability to differentiate into the trophoblast lineage after stimulation with BMP2/BMP4. We further carried out comparative transcriptome analyses of primary human AFCs, AFiPSCs, fibroblast-derived iPSCs (FiPSCs) and embryonic stem cells (ESCs). This revealed that the expression of key senescence-associated genes are down-regulated upon the induction of pluripotency in primary AFCs (AFiPSCs). By defining distinct and overlapping gene expression patterns and deriving the LARGE (Lost, Acquired and Retained Gene Expression) Principle of Cellular Reprogramming, we could further highlight that AFiPSCs, FiPSCs and ESCs share a core self-renewal gene regulatory network driven by OCT4, SOX2 and NANOG. Nevertheless, these cell types are marked by distinct gene expression signatures. For example, expression of the transcription factors, SIX6, EGR2, PKNOX2, HOXD4, HOXD10, DLX5 and RAXL1, known to regulate developmental processes, are retained in AFiPSCs and FiPSCs. Surprisingly, expression of the self-renewal-associated gene PRDM14 or the developmental processes-regulating genes WNT3A and GSC are restricted to ESCs. Implications of this, with respect to the stability of the undifferentiated state and long-term differentiation potential of iPSCs, warrant further studies.

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