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Stem cell biology

A novel slug-containing negative-feedback loop regulates SCF/c-Kit-mediated hematopoietic stem cell self-renewal

Leukemia volume 31, pages 403–413 (2017)Cite this article

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Abstract

The stem cell factor (SCF)/c-Kit pathway has crucial roles in controlling hematopoietic stem cell (HSC) renewal. However, little is known about the intracellular regulation of the SCF/c-Kit pathway in HSCs. We report here that Slug, a zinc-finger transcription repressor, functions as a direct transcriptional repressor of c-Kit in HSCs. Conversely, SCF/c-Kit signaling positively regulates Slug through downstream c-Myc and FoxM1 transcription factors. Intriguingly, c-Kit expression is induced by SCF/c-Kit signaling in Slug-deficient HSCs. The balance between Slug and c-Kit is critical for maintaining HSC repopulating potential in vivo. Together, our studies demonstrate that Slug functions in a novel negative-feedback regulatory loop in the SCF/c-Kit signaling pathway in HSCs.

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Acknowledgements

This work was supported by NIH grants DK090478 and AG040182. We thank the Flow Cytometry Core and the Biological Resources Laboratory at University of Illinois at Chicago.

Author contributions

ZZ and W-SW designed and interpreted all experiments. ZZ planed and conducted most of the experiments. YZ conducted microarray analysis. PZ, YS, YH, ZQ and DX contributed to animal studies. ZZ, JM and W-SW wrote the manuscript.

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  1. Division of Hematology/Oncology, Department of Medicine, UI Cancer Center, University of Illinois at Chicago, Chicago, IL, USA

    Z Zhang, P Zhu, Y Zhou, Y Sheng, Y Hong, D Xiang, Z Qian, J Mosenson & W-S Wu

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  1. Z Zhang
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Correspondence to W-S Wu.

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Zhang, Z., Zhu, P., Zhou, Y. et al. A novel slug-containing negative-feedback loop regulates SCF/c-Kit-mediated hematopoietic stem cell self-renewal. Leukemia 31, 403–413 (2017). https://doi.org/10.1038/leu.2016.201

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