title: Next generation of ALDH substrates and their potential to study maturational lineage biology in stem and progenitor cells.
abstract: 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.
authors: Liver Cell Biology Lab, Vrije Universiteit Brussel (VUB), Brussels, Belgium; ldolle@vub.ac.be.
authors: Laurent
authors: L
authors: Dollé
authors: MRC Human Genetics Unit, Institute for Genetics and Molecular Medicine, Edinburgh, United Kingdom; and.
authors: Luke
authors: L
authors: Boulter
authors: Laboratory of Hepato-Gastroenterology, Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain (UCL), Brussels, Belgium.
authors: Isabelle A
authors: IA
authors: Leclercq
authors: Liver Cell Biology Lab, Vrije Universiteit Brussel (VUB), Brussels, Belgium;
authors: Leo A
authors: LA
authors: van Grunsven
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002469:Cell Separation / Q000379:methods*; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes; D010641:Phenotype; D013234:Stem Cells / Q000201:enzymology*; D013379:Substrate Specificity; D013997:Time Factors
chemical_list: D015415:Biomarkers; D005456:Fluorescent Dyes; D007527:Isoenzymes; D000444:Aldehyde Dehydrogenase
keywords: ALDH activity; AldeRed-588-A; Aldefluor; liver progenitor cell
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