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Slc20a1b is essential for hematopoietic stem/progenitor cell expansion in zebrafish

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Abstract

Hematopoietic stem and progenitor cells (HSPCs) are able to self-renew and can give rise to all blood lineages throughout their lifetime, yet the mechanisms regulating HSPC development have yet to be discovered. In this study, we characterized a hematopoiesis defective zebrafish mutant line named smu07, which was obtained from our previous forward genetic screening, and found the HSPC expansion deficiency in the mutant. Positional cloning identified that slc20a1b, which encodes a sodium phosphate cotransporter, contributed to the smu07 blood phenotype. Further analysis demonstrated that mutation of slc20a1b affects HSPC expansion through cell cycle arrest at G2/M phases in a cell-autonomous manner. Our study shows that slc20a1b is a vital regulator for HSPC proliferation in zebrafish early hematopoiesis and provides valuable insights into HSPC development.

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Data availability

All relevant data are included in the manuscript, figures, and supplementary materials. The RNA-Seq raw data were submitted to the GEO repository (GSE165415).

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Acknowledgements

This work was supported by the National Key Research and Development Program of China (2018YFA0800200), the National Natural Science Foundation of China (31922023), China Postdoctoral Science Foundation (2018M643071), Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2019), and the Fundamental Research Funds for the Central Universities (2019ZD54 and 2019MS131). We thank Dr. Jingwei Xiong and Dr. Bo Zhang for sharing CRISPR/Cas9-related material (gRNA-pMD19-T) and protocols, and Dr. Tingxi Liu for sharing with us the Tg(mpx:eGFP) lines. We also thank Dr. Jianbin Wang for sharing with us the methodology for mini-bulk RNA-Seq.

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Correspondence to Wenqing Zhang or Yiyue Zhang.

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Chen, J., Li, G., Lian, J. et al. Slc20a1b is essential for hematopoietic stem/progenitor cell expansion in zebrafish. Sci. China Life Sci. 64, 2186–2201 (2021). https://doi.org/10.1007/s11427-020-1878-8

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  • DOI: https://doi.org/10.1007/s11427-020-1878-8

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