A miR-34a-Numb Feedforward Loop Triggered by Inflammation Regulates Asymmetric Stem Cell Division in Intestine and Colon Cancer.
Abstract
Emerging evidence suggests that microRNAs can initiate asymmetric division, but whether
microRNA and protein cell fate determinants coordinate with each other remains unclear.
Here, we show that miR-34a directly suppresses Numb in early-stage colon cancer stem
cells (CCSCs), forming an incoherent feedforward loop (IFFL) targeting Notch to separate
stem and non-stem cell fates robustly. Perturbation of the IFFL leads to a new intermediate
cell population with plastic and ambiguous identity. Lgr5+ mouse intestinal/colon
stem cells (ISCs) predominantly undergo symmetric division but turn on asymmetric
division to curb the number of ISCs when proinflammatory response causes excessive
proliferation. Deletion of miR-34a inhibits asymmetric division and exacerbates Lgr5+
ISC proliferation under such stress. Collectively, our data indicate that microRNA
and protein cell fate determinants coordinate to enhance robustness of cell fate decision,
and they provide a safeguard mechanism against stem cell proliferation induced by
inflammation or oncogenic mutation.
Type
Journal articleSubject
AnimalsAsymmetric Cell Division
Base Sequence
Cell Differentiation
Cell Lineage
Cell Proliferation
Gene Knockdown Techniques
Inflammation
Membrane Proteins
Mice
MicroRNAs
Molecular Sequence Data
Neoplastic Stem Cells
Nerve Tissue Proteins
Receptors, Notch
Stress, Physiological
Tumor Necrosis Factor-alpha
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https://hdl.handle.net/10161/11645Published Version (Please cite this version)
10.1016/j.stem.2016.01.006Publication Info
Bu, Pengcheng; Wang, Lihua; Chen, Kai-Yuan; Srinivasan, Tara; Murthy, Preetish Kadur
Lakshminarasimha; Tung, Kuei-Ling; ... Shen, Xiling (2016). A miR-34a-Numb Feedforward Loop Triggered by Inflammation Regulates Asymmetric Stem
Cell Division in Intestine and Colon Cancer. Cell Stem Cell, 18(2). pp. 189-202. 10.1016/j.stem.2016.01.006. Retrieved from https://hdl.handle.net/10161/11645.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Xiling Shen
Adjunct Professor in the Department of Pathology
Dr. Shen’s research interests lie at precision medicine and systems biology. His lab
integrates engineering, computational and biological techniques to study cancer, stem
cells, microbiota and the nervous system in the gut. This multidisciplinary work has
been instrumental in initiating several translational clinical trials in precision
therapy. He is the director of the Woo Center for Big Data and Precision Health (DAP)
and a core member of the Center for Genomics and Computational Biolog

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