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造血干细胞龛的分子特征。

A molecular profile of a hematopoietic stem cell niche.

作者信息

Hackney Jason A, Charbord Pierre, Brunk Brian P, Stoeckert Christian J, Lemischka Ihor R, Moore Kateri A

机构信息

Department of Molecular Biology, Princeton University, Princeton, NJ 08544; Laboratoire d'Hematopoièse, Faculté de Médecine, Université de Tours, 37041 Tours Cedex 1, France.

出版信息

Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):13061-6. doi: 10.1073/pnas.192124499. Epub 2002 Sep 11.

Abstract

The hematopoietic microenvironment provides a complex molecular milieu that regulates the self-renewal and differentiation activities of stem cells. We have characterized a stem cell supportive stromal cell line, AFT024, that was derived from murine fetal liver. Highly purified in vivo transplantable mouse stem cells are maintained in AFT024 cultures at input levels, whereas other primitive progenitors are expanded. In addition, human stem cells are very effectively supported by AFT024. We suggest that the AFT024 cell line represents a component of an in vivo stem cell niche. To determine the molecular signals elaborated in this niche, we undertook a functional genomics approach that combines extensive sequence mining of a subtracted cDNA library, high-density array hybridization and in-depth bioinformatic analyses. The data have been assembled into a biological process oriented database, and represent a molecular profile of a candidate stem cell niche.

摘要

造血微环境提供了一个复杂的分子环境,可调节干细胞的自我更新和分化活性。我们已鉴定出一种干细胞支持性基质细胞系AFT024,它源自小鼠胎儿肝脏。高度纯化的可在体内移植的小鼠干细胞在AFT024培养物中维持在输入水平,而其他原始祖细胞则得以扩增。此外,AFT024能非常有效地支持人类干细胞。我们认为AFT024细胞系代表了体内干细胞龛的一个组成部分。为了确定在这个龛中产生的分子信号,我们采用了一种功能基因组学方法,该方法结合了对消减cDNA文库的广泛序列挖掘、高密度阵列杂交和深入的生物信息学分析。这些数据已被整合到一个以生物过程为导向的数据库中,代表了一个候选干细胞龛的分子概况。

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