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A miR-34a-Numb Feedforward Loop Triggered by Inflammation Regulates Asymmetric Stem Cell Division in Intestine and Colon Cancer.

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Date
2016-02-04
Authors
Bu, Pengcheng
Wang, Lihua
Chen, Kai-Yuan
Srinivasan, Tara
Murthy, Preetish Kadur Lakshminarasimha
Tung, Kuei-Ling
Varanko, Anastasia Kristine
Chen, Huanhuan Joyce
Ai, Yiwei
King, Sarah
Lipkin, Steven M
Shen, Xiling
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(12 total)
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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 article
Subject
Animals
Asymmetric 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
Permalink
https://hdl.handle.net/10161/11645
Published Version (Please cite this version)
10.1016/j.stem.2016.01.006
Publication 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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Scholars@Duke

Shen

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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