Next generation of ALDH substrates and their potential to study maturational lineage biology in stem and progenitor cells.
Bottom Line: 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.
Affiliation: Liver Cell Biology Lab, Vrije Universiteit Brussel (VUB), Brussels, Belgium; firstname.lastname@example.org.Show MeSH
Related in: MedlinePlus
Mentions: By their recent publication in Nature Communications, Minn and collaborators (21) rejuvenated the interest in using ALDH activity. They described a new red-shifted fluorescent ALDH substrate (AldeRed-588-A), for labeling of viable ALDHbright cell populations. Structurally, Aldefluor (or Bodipy493/503-aminoacetaldehyde) and AldeRed-588-A (or Bodipy576/589-aminoacetaldehyde) have a common substrate moiety: acetaldehyde, indicating that a cell oxidizing Aldefluor is likely to have the same ability to metabolize the AldeRed-588-A substrate (Fig. 1A). In other words, AldeRed-588-A is considered as one of the other alternatives to Aldefluor substrate, without other functionally different characteristics. Elegantly, using cell lines known to express functional ALDH the authors demonstrated that Aldefluor and AldeRed-588-A essentially have the same efficacy and efficiency for identifying a ALDHbright population (21). In addition, by successfully mixing two substrates, Minn and colleagues prove that labeling technique does not impede the structural recognition of the substrate by ALDH enzyme and that cell isolation of ALDH expressing cells is feasible by a single-step isolation method (Aldefluor and AldeRed-588-A are incubated simultaneously), thus avoiding additional purification or enrichment steps in which cells can be lost or damaged. This new AldeRed-588-A substrate has a broad emission spectrum, which currently precludes combination with a large array of fluorophores. Nevertheless, the technical innovation opens new avenues for stem cell research by offering a greater flexibility for ALDHbright cell isolations.
Affiliation: Liver Cell Biology Lab, Vrije Universiteit Brussel (VUB), Brussels, Belgium; email@example.com.