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NORMAL HEMATOPOIESIS

Erythropoietin receptor contributes to thrombopoietin receptor (Mpl)-independent thrombocytopoiesis in zebrafish

Leukemia volume 36, pages 1193–1197 (2022)Cite this article

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Platelets/thrombocytes play crucial roles in hemostasis and thrombosis [1]. Platelets and red blood cells are thought to share a common bipotent megakaryocytic and erythroid progenitor during mammalian hematopoiesis, mainly derived from hematopoietic stem cells [2]. The primary pathway for thrombocytopoiesis is the thrombopoietin (THPO)/THPO receptor (MPL) pathway [3], and Thpo−/− and Mpl−/− mice, and mplsmu3 zebrafish show severe thrombocytopenia [4, 5]. However, Mpl-independent thrombocytopoiesis remains largely unexplored. Several cytokine pathways, such as interleukin (IL)−3, IL-6, IL-11, and leukemia inhibitory factor, have previously been reported to be involved in thrombocyte generation and have been shown to induce thrombopoiesis, while none of them are the source for Mpl-independent thrombocytopoiesis [6, 7].

The erythropoietin (EPO)/EPO receptor (EPOR) is essential for erythropoiesis [8], and some evidence suggests that it also plays a potential role in thrombocytopoiesis. Several studies have shown the potential of EPO to induce megakaryocyte colony formation in vitro, and EPO has demonstrated modest effects on platelet reactivity and thrombocytopoiesis in vivo [9]. Functional clearance of EPO by antibody neutralization resulted in further reduction of residual platelets in Thpo−/− and Mpl−/−adult mice [10]. Epo−/− and Epor−/− mice are embryonic lethal, and in vivo genetic data for the role of the EPO/EPOR pathway as an Mpl-independent source of thrombocyte production is thus still lacking. Further studies are therefore needed to determine the potential collaboration and competition between the EPO/EPOR and THPO/MPL pathways in thrombocytopoiesis. Here, we investigated the synergistic effects of mpl and epor in thrombocytopoiesis in zebrafish.

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Fig. 1: epor was enriched in a subset of zebrafish thrombocytic progenitors.
Fig. 2: epor is essential for mpl-independent thrombocytopoiesis and epo expanded thrombocytes by activating Jak2.

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Acknowledgements

We would like to thank Mr. Xiaohui Chen and Ms. Li Song for helping with the fish facility maintenance and the technique supports, and Mr. Dejian Zhao for his suggestion on data collection. This work was supported by National Natural Science Foundation of China (81870100 and 31871475), the National Key R&D Program of China (2018YFA0800200), Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2019).

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  1. These authors contributed equally: Qing Lin, Junwei Lian.

Authors and Affiliations

  1. Division of Cell, Developmental and Integrative Biology, School of Medicine, South China University of Technology, Guangzhou, 510006, P. R. China

    Qing Lin, Junwei Lian, Jiaye Wu, Panpan Meng, Liangliang Wu & Yiyue Zhang

  2. Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, P. R. China

    Ying Sun

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Contributions

YYZ, QL designed the study. QL, JWL, JYW, PPM, YS performed experiments. QL, JWL, LLW analyzed and organized data. JWL drafted the manuscript. YYZ, QL, JWL revised the final manuscript.

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Correspondence to Yiyue Zhang.

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Lin, Q., Lian, J., Wu, J. et al. Erythropoietin receptor contributes to thrombopoietin receptor (Mpl)-independent thrombocytopoiesis in zebrafish. Leukemia 36, 1193–1197 (2022). https://doi.org/10.1038/s41375-021-01495-9

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