Aldehyde dehydrogenase 1a1 is dispensable for stem cell function in the mouse hematopoietic and nervous systems

Boaz P. Levi, Ömer H. Yilmaz, Gregg Duester, Sean J. Morrison

Research output: Contribution to journalArticle

74 Citations (Scopus)

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 metabolisminthe 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.

Original languageEnglish (US)
Pages (from-to)1670-1680
Number of pages11
JournalBlood
Volume113
Issue number8
DOIs
StatePublished - Feb 19 2009

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Hematopoietic System
Aldehyde Dehydrogenase
Neurology
Stem cells
Nervous System
Adult Stem Cells
Stem Cells
Hematopoietic Stem Cells
Cyclophosphamide
Staining and Labeling
Neural Stem Cells
Neoplastic Stem Cells
Hematopoiesis
Peripheral Nervous System
Fluorescent Dyes
Central Nervous System
Liver
Enzymes

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Aldehyde dehydrogenase 1a1 is dispensable for stem cell function in the mouse hematopoietic and nervous systems. / Levi, Boaz P.; Yilmaz, Ömer H.; Duester, Gregg; Morrison, Sean J.

In: Blood, Vol. 113, No. 8, 19.02.2009, p. 1670-1680.

Research output: Contribution to journalArticle

Levi, Boaz P. ; Yilmaz, Ömer H. ; Duester, Gregg ; Morrison, Sean J. / Aldehyde dehydrogenase 1a1 is dispensable for stem cell function in the mouse hematopoietic and nervous systems. In: Blood. 2009 ; Vol. 113, No. 8. pp. 1670-1680.
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