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本帖最后由 hyde 于 2010-12-24 16:36 编辑 & Y" W# R( \ ~' S
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Comparative analysis of human Embryonic Stem Cell and induced Pluripotent Stem Cell-derived hepatocyte-like cells reveals current drawbacks and possible strategies for improved differentiation( J1 b) O. b- ]! ]1 g
原文来源自Mary Ann Liebert, http://www.liebertonline.com/doi/abs/10.1089/scd.2010.0361; l5 D5 Y `# I
由干细胞之家新闻小组成员Hyde翻译（转帖请注明）
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To cite this article:
4 L5 T/ @: U: h6 X. NJustyna Jozefczuk, Alessandro Prigione, Lukas Chavez, James Adjaye. Stem Cells and Development. -Not available-, ahead of print. doi:10.1089/scd.2010.0361.
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' m' K ?. o5 J. l; L; NOnline Ahead of Editing: December 16, 20107 J9 E0 L+ \5 r4 T i1 k6 u% Q
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Dr. Justyna Jozefczuk, Ph.D.
; r6 H. J) l7 M* uMax Planck Institute for Molecular Genetics, Vertebrate Genomics, Ihnestrasse 63-73, Berlin, Germany, 14195, 00493084131237, 00493084131394; jagodzin@molgen.mpg.de# {8 @% {* M( [2 e' n
Dr. Alessandro Prigione
2 e# }' z9 C' Z: R& iMax Planck Institute for Molecular Genetics, Vertebrate Genomics, Berlin, Germany; prigione@molgen.mpg.de5 p% f) T) o+ {% R( D
Mr. Lukas Chavez3 k/ g9 r) l# j
Max Planck Institute for Molecular Genetics, Vertebrate Genomics, Berlin, Germany; chavez@molgen.mpg.de
' I8 U2 B9 h1 _ A+ U8 CDr. James Adjaye% F9 S2 ], e9 ~+ B1 F6 G. n
Max Planck Institute for Molecular Genetics, Vertebrate Genomics, Berlin, Germany; adjaye@molgen.mpg.de2 H5 C: n7 Q) k& S( a
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使用HES或IPS诱导出肝细胞为细胞治疗和毒理学研究提供了一个可靠而又具有自我更新能力的细胞来源。但是在使用病人细胞做相关应用之前，我们还需要将这些肝细胞与一个黄金标准hES进行比较。我们研究的目的在于调查不同来源（hES和IPS）获得的肝脏类似细胞在转录水平上的不同点和相似点。我们选择了两个独立的实验过程分别使用hESCs 和 iPSCs 来诱导出肝脏类似细胞，随后进行进一步的鉴定：免疫细胞化学、实时定量反转率PCR、体外功能性分析。使用基因芯片对两种细胞的基因表达情况进行比较，同时与胎儿肝脏和成体肝脏前体细胞的转录情况进行比较。来源于 hESCs 和hiPSCs 的肝脏类似细胞具有高度的功能相似性，相似的基因表达对于维持肝脏的生理功能和生理途径是非常重要的。但是这两种细胞之间还是存在着明显的差异。比如说：细胞色素基因cytochrome P450 家族在这两种细胞中的表达偏好型不同，hESCs来源的大量表达CYP19A1, CYP1A1, 和CYP11A1 ，而 iPSCs来源的大量表达CYP46A1, CYP26A1。综上所述可见不同来源的肝脏来使细胞存在着广泛的相似性和微妙的差异性。我们发现了一些普遍上调的转录因子，这些可以作为候选因子用于研究由体细胞到肝脏细胞的直接诱导转化。这一发现对于完善诱导获得病人的肝脏类似细胞的操作过程很有意义，可用于再生和毒理研究。+ r3 ]7 _; O u4 H$ ~( ~ \8 a$ u" q
: ~1 [" h% B) c- \+ r0 OHepatocytes derived from human embryonic stem cells (hESCs) or induced pluripo-tent stem cells (iPSCs) could provide a defined and renewable source of human cells relevant for cell replacement therapies and toxicology studies. However, before patient-specific iPSCs can be routinely used for these purposes, there is a dire need to critically compare these cells to the golden standard - hESCs. In this study, we aimed at investigating the differences and similarities at the transcriptional level between hepatocyte-like cells (HLCs) derived from both hESCs and iPSCs. Two independent protocols for deriving HLCs from hESCs and iPSCs were adopted and further characterization included immunocytochemistry, real-time RT-PCR, and in vitro functional assays. Comparative microarray-based gene expression profiling was conducted on these cells and compared to the transcriptomes of human fetal liver and adult liver progenitors. HLCs derived from hESCs and hiPSCs showed significant functional similarities, similar expression of genes important for liver physiology and common pathways. However, specific differences between the two cell types could be observed. For example, amongst the cytochrome P450 gene family, CYP19A1, CYP1A1, and CYP11A1 were enriched in hESCs-derived HLCs and CYP46A1, CYP26A1 in iPSCs-derived HLCs. HLCs derived from hESCs and hiPSCs exhibited broad similarities and subtle differ-ences. We identified common up-regulated transcription factors, which might serve as a source for generating a cocktail of factors able to directly trans-differentiate somatic cells into HLCs. The findings may be vital to the refinement of protocols for the efficient derivation of functional patient-specific HLCs for regenerative and toxicology studies.
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* u0 l3 P g" a原文附件
' m+ g- C+ f& M6 f注明：个人翻译，理解不准确的语句还望大家积极指出 |
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发表于 2010-12-24 16:35
