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Normal Hemopoiesis

A DEAB-sensitive aldehyde dehydrogenase regulates hematopoietic stem and progenitor cells development during primitive hematopoiesis in zebrafish embryos

Leukemia volume 24, pages 2090–2099 (2010)Cite this article

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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.

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Acknowledgements

We thank Dr Anming Meng (Tsinghua University, China) for the generous gift of the Tg(gata1:gfp) fish-lines. The works were supported by the General Research Fund (HKU 752006M, 770308M and 769809M), the Seed Funding Programme for Basic Research (200711159060), Small Project Funding to ACH Ma (200907176072) and Seed Funding Programme for Basic Research to R Liang (200611159093) as well as a grant from the strategy research theme of cancer stem cells in the University of Hong Kong.

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  1. Division of Haematology and Bone Marrow Transplantation, Department of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR

    A C H Ma, M I S Chung, R Liang & A Y H Leung

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  1. A C H Ma
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  2. M I S Chung
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Correspondence to A Y H Leung.

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Ma, A., Chung, M., Liang, R. et al. A DEAB-sensitive aldehyde dehydrogenase regulates hematopoietic stem and progenitor cells development during primitive hematopoiesis in zebrafish embryos. Leukemia 24, 2090–2099 (2010). https://doi.org/10.1038/leu.2010.206

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