Sparse feature selection identifies H2A.Z as a novel, pattern-specific biomarker for asymmetrically self-renewing distributed stem cells.

Sparse feature selection identifies H2A.Z as a novel, pattern-specific biomarker for asymmetrically self-renewing distributed stem cells.
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DOI:
10.1016/j.scr.2014.12.007
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发表时间:
2015-03
期刊:
影响因子:
1.2
通讯作者:
Sherley, James L.
Sherley, James L.
中科院分区:
医学4区
文献类型:
--
作者:
Huh, Yang Hoon;Noh, Minsoo;Burden, Frank R.;Chen, Jennifer C.;Winkler, David A.;Sherley, James L.

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长期以来,对组织中的分布式干细胞(DSC)具有高特异性的生物标志物或用于诊断和治疗性细胞制剂(例如,骨髓)。尽管DSC对于组织维护和修复是必不可少的,但用于医学应用的其数量的准确确定一直是有问题的。以前对在DSCs中特异性表达的生物标志物的搜索受到难以获得纯DSCs和挖掘复杂分子表达数据的挑战的阻碍。为了鉴定DSC这种有用的和特异性的生物标志物,我们将一种新的稀疏特征选择方法与组合分子表达数据相结合,该组合分子表达数据集中于不对称自我更新,这是DSC的一个显著特性。该分析鉴定了组蛋白H2A变体H2A. Z的表达减少作为DSC不对称自我更新的上级分子标记。随后的分子表达研究表明,H2A.Z是一种新的“模式特异性生物标志物”,用于不对称自我更新细胞,具有足够的特异性,可以在体外和潜在的原位计数不对称自我更新的DSC。
There is a long-standing unmet clinical need for biomarkers with high specificity for distributed stem cells (DSCs) in tissues, or for use in diagnostic and therapeutic cell preparations (e.g., bone marrow). Although DSCs are essential for tissue maintenance and repair, accurate determination of their numbers for medical applications has been problematic. Previous searches for biomarkers expressed specifically in DSCs were hampered by difficulty obtaining pure DSCs and by the challenges in mining complex molecular expression data. To identify DSC such useful and specific biomarkers, we combined a novel sparse feature selection method with combinatorial molecular expression data focused on asymmetric self-renewal, a conspicuous property of DSCs. The analysis identified reduced expression of the histone H2A variant H2A.Z as a superior molecular discriminator for DSC asymmetric self-renewal. Subsequent molecular expression studies showed H2A.Z to be a novel “pattern-specific biomarker” for asymmetrically self-renewing cells with sufficient specificity to count asymmetrically self-renewing DSCs in vitro and potentially in situ.
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