PUBLICATION
A DEAB-sensitive aldehyde dehydrogenase regulates hematopoietic stem and progenitor cells development during primitive hematopoiesis in zebrafish embryos
- Authors
- Ma, A.C., Chung, M.I., Liang, R., and Leung, A.Y.
- ID
- ZDB-PUB-101018-3
- Date
- 2010
- Source
- Leukemia 24(12): 2090-2099 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Aldehyde Dehydrogenase/antagonists & inhibitors
- Aldehyde Dehydrogenase/physiology*
- Animals
- Cell Differentiation/drug effects
- Enzyme Inhibitors/pharmacology*
- Gene Expression Profiling
- Gene Expression Regulation, Developmental/drug effects
- Hematopoiesis/drug effects*
- Hematopoietic Stem Cells/drug effects*
- Hematopoietic Stem Cells/physiology
- Tretinoin/pharmacology
- Zebrafish/embryology*
- PubMed
- 20927131 Full text @ Leukemia
Citation
Ma, A.C., Chung, M.I., Liang, R., and Leung, A.Y. (2010) A DEAB-sensitive aldehyde dehydrogenase regulates hematopoietic stem and progenitor cells development during primitive hematopoiesis in zebrafish embryos. Leukemia. 24(12):2090-2099.
Abstract
Although aldehyde dehydrogenase (ALDH) activity has become a surrogate of hematopoietic stem and progenitor cells (HSPCs), its function during hematopoiesis was unclear. Here, we examined its role in zebrafish hematopoiesis based on pharmacological inhibition and morpholino (MO) knockdown. Zebrafish embryos were treated with diethylaminobenzaldehyde (DEAB, 1 μmol/l) between 0- and 48 hour-post-fertilization (hpf). MOs targeting aldhs were injected between 1 and 4-cell stage. The effects on hematopoiesis were evaluated at different stages. DEAB treatment between 0 and 18 hpf increased gene expression associated with HSPC (scl, lmo2), erythropoiesis (gata1, α- and β-eHb) and myelopoiesis (spi1) as well as gfp(+) cells in dissociated Tg(gata1:gfp) embryos. The effects were ameliorated by all-trans retinoic acid (1 nmol/l). Definitive hematopoiesis and the erythromyeloid precursors were unaffected. In all, 14 out of 15 zebrafish aldhs were detectable by reverse transcription PCR in 18 hpf embryos, of which only aldh1a2 and aldh16a1 were expressed in sites pertinent to hematopoiesis. Molecular targeting by MOs was demonstrated for 15 aldhs, but none of them, even in combined aldh1a2 and aldh1a3 knockdown, recapitulated the hematopoietic expansion in DEAB-treated embryos. In conclusion, DEAB expands HSPC population during primitive hematopoiesis through inhibition of aldh and retinoic acid synthesis. The specific aldh isoform(s) remains to be determined.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping