Next generation of ALDH substrates and their potential to study maturational lineage biology in stem and progenitor cells.

Next generation of ALDH substrates and their potential to study maturational lineage biology in stem and progenitor cells.
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DOI:
10.1152/ajpgi.00420.2014
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发表时间:
2015-04-01
期刊:
American journal of physiology. Gastrointestinal and liver physiology
影响因子:
--
通讯作者:
van Grunsven LA
van Grunsven LA
中科院分区:
其他
文献类型:
--
作者:
Dollé L;Boulter L;Leclercq IA;van Grunsven LA

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高醛脱氢酶(ALDH)活性是来自正常组织和肿瘤组织的干细胞的一个特征,也是分离它们的可靠的通用标记。根据组织、细胞类型、细胞器和细胞状态的不同,有许多具有首选底物特异性的ALDH亚型表达。另一方面,一种特定的底物可能被几种同工酶代谢。目前,ALDH活性的证据是使用Aldeflor,一种可能被多种ALDH亚型代谢的荧光底物。因此,基于ALDH活性检测的分离技术选择了一个不同的干细胞或祖细胞群体。尽管该领域的研究很活跃,但不同的乳酸脱氢酶亚型在干细胞中的确切作用(S)仍然是个谜。了解不同的ALDH异构体在控制干细胞表型和细胞发育、组织内稳态或修复以及癌变过程中的代谢作用,将为组织生物学的重大发现开辟新的前景。从这个角度来看,人们正在开发新型的ALDH衬底。在这里,我们描述了新的底物如何有助于更好地分离具有干细胞潜力的细胞群体,并定义组织中细胞群体的层次结构。最后,我们推测了其他潜在的应用。
High aldehyde dehydrogenase (ALDH) activity is a feature of stem cells from normal and cancerous tissues and a reliable universal marker used to isolate them. There are numerous ALDH isoforms with preferred substrate specificity variably expressed depending on tissue, cell type, and organelle and cell status. On the other hand, a given substrate may be metabolized by several enzyme isoforms. Currently ALDH activity is evidenced by using Aldefluor, a fluorescent substrate likely to be metabolized by numerous ALDH isoforms. Therefore, isolation techniques based on ALDH activity detection select a heterogeneous population of stem or progenitor cells. Despite active research in the field, the precise role(s) of different ALDH isoforms in stem cells remains enigmatic. Understanding the metabolic role of different ALDH isoform in the control of stem cell phenotype and cell fate during development, tissue homeostasis, or repair, as well as carcinogenesis, should open perspectives to significant discoveries in tissue biology. In this perspective, novel ALDH substrates are being developed. Here we describe how new substrates could be instrumental for better isolation of cell population with stemness potential and for defining hierarchy of cell populations in tissue. Finally, we speculate on other potential applications.
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