期刊
LEUKEMIA
卷 24, 期 12, 页码 2090-2099出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/leu.2010.206
关键词
aldehyde dehydrogenase; zebrafish; hematopoiesis; hematopoietic stem cells
资金
- Seed Funding Programme for Basic Research [200711159060, 200611159093]
- Small Project Funding [200907176072]
- University of Hong Kong
- General Research Fund (HKU) [752006M, 770308M, 769809M]
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 mu mol/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, alpha-a nd beta-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. Leukemia (2010) 24, 2090-2099; doi:10.1038/leu.2010.206; published online 7 October 2010
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