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人类胎儿肝脏与成人骨髓间充质干细胞之间的基因表达差异。

Difference in gene expression between human fetal liver and adult bone marrow mesenchymal stem cells.

作者信息

Götherström Cecilia, West Anne, Liden Johan, Uzunel Mehmet, Lahesmaa Riitta, Le Blanc Katarina

机构信息

Division of Clinical Immunology, F79, Karolinska University Hospital Huddinge, SE-141 86 Stockholm, Sweden.

出版信息

Haematologica. 2005 Aug;90(8):1017-26.

Abstract

BACKGROUND AND OBJECTIVES

Mesenchymal stem cells (MSC) are progenitor cells that are capable of differentiating into mesenchymal tissues. Fetal and adult MSC have similar morphology but differ in proliferative, differentiating and immunosuppressive properties. Further exploring their differences could help in choosing the right source for cellular therapy.

DESIGN AND METHODS

The gene expression profiles of undifferentiated MSC derived from first trimester fetal liver and adult bone marrow were compared by serial analysis of gene expression, and validated by either reverse transcription polymerase chain reaction or immunoblotting of selected genes. The immunophenotype was compared by flow cytometry and cell ELISA.

RESULTS

Seventy genes were differentially induced two-fold or more in fetal MSC compared to adult MSC. These involved transcripts regulating germ plasm and limb patterning, brain and early muscle development. Transcripts implicated in cell cycle promotion, chromatin regulation and DNA repair were also more abundant in fetal MSC. Ninety-seven genes were decreased two-fold or more in fetal MSC, including transcripts involved in smooth muscle and keratinocyte differentiation and transcripts for immunological genes. Although phenotypically largely similar, fetal MSC had a higher expression of ICAM1 and contained intracellular deposits of HLA-G while expression of HLA class I and II molecules and VCAM1 was increased in adult MSC.

INTERPRETATION AND CONCLUSIONS

This study reports the first extensive investigation of the differences in gene expression profiles between fetal and adult MSC. The results suggest that fetal MSC have higher proliferative capacity and are less lineage committed than adult MSC.

摘要

背景与目的

间充质干细胞(MSC)是能够分化为间充质组织的祖细胞。胎儿和成人的MSC具有相似的形态,但在增殖、分化和免疫抑制特性方面存在差异。进一步探究它们的差异有助于为细胞治疗选择合适的细胞来源。

设计与方法

通过基因表达序列分析比较了来自孕早期胎儿肝脏和成人骨髓的未分化MSC的基因表达谱,并通过逆转录聚合酶链反应或对选定基因进行免疫印迹进行验证。通过流式细胞术和细胞酶联免疫吸附测定比较免疫表型。

结果

与成人MSC相比,胎儿MSC中有70个基因的差异诱导倍数达到两倍或更高。这些基因涉及调控种质和肢体模式、脑和早期肌肉发育的转录本。与细胞周期促进、染色质调控和DNA修复相关的转录本在胎儿MSC中也更为丰富。胎儿MSC中有97个基因的表达降低了两倍或更多,包括参与平滑肌和角质形成细胞分化的转录本以及免疫基因的转录本。尽管在表型上基本相似,但胎儿MSC中ICAM1的表达较高,且含有HLA - G的细胞内沉积物,而成人MSC中HLA I类和II类分子以及VCAM1的表达增加。

解读与结论

本研究首次广泛调查了胎儿和成人MSC基因表达谱的差异。结果表明,与成人MSC相比,胎儿MSC具有更高的增殖能力,且细胞谱系定向程度较低。

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