title: Aldehyde dehydrogenase 1a1 is dispensable for stem cell function in the mouse hematopoietic and nervous systems.
abstract: High levels of aldehyde dehydrogenase (ALDH) activity have been proposed to be a common feature of stem cells. Adult hematopoietic, neural, and cancer stem cells have all been reported to have high ALDH activity, detected using Aldefluor, a fluorogenic substrate for ALDH. This activity has been attributed to Aldh1a1, an enzyme that is expressed at high levels in stem cells and that has been suggested to regulate stem cell function. Nonetheless, Aldh1a1 function in stem cells has never been tested genetically. We observed that Aldh1a1 was preferentially expressed in mouse hematopoietic stem cells (HSCs) and expression increased with age. Hematopoietic cells from Aldh1a1-deficient mice exhibited increased sensitivity to cyclophosphamide in a non-cell-autonomous manner, consistent with its role in cyclophosphamide metabolism in the liver. However, Aldh1a1 deficiency did not affect hematopoiesis, HSC function, or the capacity to reconstitute irradiated recipients in young or old adult mice. Aldh1a1 deficiency also did not affect Aldefluor staining of hematopoietic cells. Finally, Aldh1a1 deficiency did not affect the function of stem cells from the adult central or peripheral nervous systems. Aldh1a1 is not a critical regulator of adult stem cell function or Aldefluor staining in mice.
authors.affiliation: Howard Hughes Medical Institute, Department of Internal Medicine, and Center for Stem Cell Biology, Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109-2216, USA.
authors.forename: Boaz P
authors.initials: BP
authors.lastname: Levi
authors.forename: Omer H
authors.initials: OH
authors.lastname: Yilmaz
authors.forename: Gregg
authors.initials: G
authors.lastname: Duester
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Morrison
mesh_terms: D000375:Aging / Q000502:physiology; D000444:Aldehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology*; D003520:Cyclophosphamide / Q000494:pharmacology; D005456:Fluorescent Dyes; D015971:Gene Expression Regulation, Enzymologic; D006410:Hematopoiesis / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D019653:Myeloablative Agonists / Q000494:pharmacology; D017933:Peripheral Nervous System / Q000166:cytology*; D050697:Retinal Dehydrogenase; D013234:Stem Cells / Q000166:cytology / Q000201:enzymology*
chemical_list: D005456:Fluorescent Dyes; D019653:Myeloablative Agonists; D003520:Cyclophosphamide; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C515028:ALDH1A1 protein, mouse; D050697:Retinal Dehydrogenase