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ABC Transporters, Aldehyde Dehydrogenase, and Adult Stem Cells

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Adult Stem Cells

Abstract

Despite many years of intensive effort, there is surprisingly little consensus on the most suitable markers with which to locate and isolate stem cells from adult tissues. So-called markers of stem cells have been varied but can be broadly categorized into molecular determinants that govern self-renewal, clonogenicity, multipotentiality, adherence to the niche and longevity. This chapter describes two specific attributes of many stem cells that appear to be the main determinants of stem cell survival, namely either an ability to detoxify many potentially cytotoxic molecules by virtue of high aldehyde dehydrogenase (ALDH) activity or an ability to actively efflux a wide variety of cytotoxic agents by virtue of the presence of one or more ATP-binding cassette transporters (ABC transporters), and indeed many stem cells may be endowed with both properties. Antibodies are available against the ALDH enzyme family and ABC transporters, but the vast majority of studies have used cell sorting techniques to enrich for cells expressing these molecules. Live cells expressing high ALDH activity are usually identified by the ALDEFLUOR kit and sorted by fluorescence-activated cell sorting (FACS), the latter technique is also being used to isolate cells with high ABC transporter activity after incubation with a fluorescent dye (usually Hoechst 33342) that is actively effluxed from these cells giving rise to a fluorescent dull population known as the “side population”. Since both ALDH and ABC transporter activities are cytoprotective strategies, it is not surprising that many cancer stem cells have these mechanisms working robustly, but they are also present in normal adult stem cells. This chapter critically reviews ALDH activity and the SP as markers of normal adult stem cells.

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Abbreviations

ABC:

ATP-binding cassette

ALDH:

Aldehyde dehydrogenase

BCRP1:

Breast cancer resistance protein

DAPI:

Diaminophenylindole

DEAB:

Diethylaminobenzaldehyde

FACS:

Fluorescence-activated cell sorting

Ho:

Hoechst

HSC:

Hematopoietic stem cell

hUCB:

Human umbilical cord blood

MDR:

Multidrug resistance

SLAM:

Signalling lymphocytic activation molecule

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Correspondence to Malcolm R. Alison .

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Guppy, N.J., Nicholson, L.J., Alison, M.R. (2011). ABC Transporters, Aldehyde Dehydrogenase, and Adult Stem Cells. In: Phinney, D. (eds) Adult Stem Cells. Stem Cell Biology and Regenerative Medicine. Humana Press. https://doi.org/10.1007/978-1-61779-002-7_8

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