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

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.

SUBMITTER: Zhang Z

PROVIDER: S-EPMC5288275 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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

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

Leukemia 20160725 2

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 S ...[more]

PMID: 27451973

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