title: 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.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, UI Cancer Center, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, UI Cancer Center, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: P
authors.initials: P
authors.lastname: Zhu
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, UI Cancer Center, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, UI Cancer Center, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Sheng
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, UI Cancer Center, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Hong
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, UI Cancer Center, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: D
authors.initials: D
authors.lastname: Xiang
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, UI Cancer Center, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Qian
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, UI Cancer Center, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: J
authors.initials: J
authors.lastname: Mosenson
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, UI Cancer Center, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: W-S
authors.initials: WS
authors.lastname: Wu
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002454:Cell Differentiation; D000066673:Cell Self Renewal / Q000235:genetics*; D016000:Cluster Analysis; D025461:Feedback, Physiological; D000072278:Forkhead Box Protein M1 / Q000378:metabolism; D015870:Gene Expression; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D006410:Hematopoiesis / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008954:Models, Biological; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors / Q000378:metabolism*; D019089:Stem Cell Factor
chemical_list: D000072278:Forkhead Box Protein M1; D016271:Proto-Oncogene Proteins c-myc; C000604429:Snai1 protein, mouse; D000071250:Snail Family Transcription Factors; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit