由于羊水干細胞能夠生成各種類型的體細胞,，因而一直被干細胞研究者們寄予厚望,?？茖W家們期待在某一天他們能夠利用羊水干細胞治療各種疾病。然而到目前為止,，由于胚胎仍是羊水干細胞的主要來源,，因而引發(fā)了眾多的倫理學問題。
近日柏林馬克斯.普朗克分子遺傳學研究所的科學家們成功地將羊水細胞轉(zhuǎn)化為多能干細胞（iPS細胞）,。這些由羊水衍生的iPS細胞幾乎與胚胎干細胞沒有區(qū)別,。然而，它們卻能“記住”它們的起源,。研究結(jié)果在線發(fā)表在國際學術(shù)刊物《公共科學圖書館.綜合》（PLoS ONE）上,。
現(xiàn)在胚胎干細胞的特殊潛能也能被運用到多種“成熟”體細胞中（例如皮膚和毛發(fā)細胞）。通過重編程可將這些細胞轉(zhuǎn)化為“誘導多能干細胞”（iPS細胞）,。iPS細胞具有胚胎干細胞的特性,，可生成各種類型的人體細胞（多潛能），并且能夠無限增殖,。
帶有記憶的干細胞
科學家們證實羊水iPS能夠形成各種不同的人體細胞類型,。在細胞重編程過程中，各種調(diào)控干細胞發(fā)育的基因明顯地打開或保持活躍,。他們還同時發(fā)現(xiàn)誘導多能干細胞能夠記住它們原來的細胞類型,。這證實了當前其他的研究結(jié)果，即當進行自發(fā)性分化時從各種不同組織衍生的iPS細胞更傾向于跟隨它們預(yù)先注定的發(fā)育路線,。“我們還不確定這種供體細胞類型的記憶是否有可能影響醫(yī)學治療,，或是體細胞衍生的iPS將會成為最適合的治療細胞類型，”
馬克斯.普朗克分子遺傳研究所的Katharina Wolfrum謹慎地表示,。
羊水細胞相對于其他的細胞類型有著多個優(yōu)勢,。一方面，在產(chǎn)前檢查中常規(guī)采集羊水細胞能夠?qū)膊∵M行早期篩查,。在大多數(shù)情況下,，獲得的細胞總是比實際需要的要多。此外,，羊水混合物中包含著各種來自于胎兒的不同類型的細胞,，包括干細胞樣細胞。
“環(huán)境誘導的突變在遺傳上更為穩(wěn)定,。這或許意味著相比于其他的細胞類型,，對羊水細胞重編程更快速，更容易,。羊水衍生的iPS細胞極有可能能夠填補對胚胎干細胞的需要,，”馬克斯.普朗克研究所的ames Adjaye解釋說：“此外，還可在小孩出生前對采集的羊水細胞進行細胞重編程,，以備不時之需,。同時還可能幫助檢測出哪些藥物會對嬰兒產(chǎn)生影響，以及能夠為其所耐受,。在未來,，患病新生兒就能夠利用從自己身體上獲得的細胞進行疾病治療。”（生物谷Bioon.com）
生物谷推薦英文摘要：
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.
