A miR-34a-Numb Feedforward Loop Triggered by Inflammation Regulates Asymmetric Stem Cell Division in Intestine and Colon Cancer.
| dc.contributor.author | Bu, Pengcheng | |
| dc.contributor.author | Wang, Lihua | |
| dc.contributor.author | Chen, Kai-Yuan | |
| dc.contributor.author | Srinivasan, Tara | |
| dc.contributor.author | Murthy, Preetish Kadur Lakshminarasimha | |
| dc.contributor.author | Tung, Kuei-Ling | |
| dc.contributor.author | Varanko, Anastasia Kristine | |
| dc.contributor.author | Chen, Huanhuan Joyce | |
| dc.contributor.author | Ai, Yiwei | |
| dc.contributor.author | King, Sarah | |
| dc.contributor.author | Lipkin, Steven M | |
| dc.contributor.author | Shen, Xiling | |
| dc.coverage.spatial | United States | |
| dc.date.accessioned | 2016-02-26T19:45:13Z | |
| dc.date.issued | 2016-02-04 | |
| dc.description.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. | |
| dc.identifier | ||
| dc.identifier | S1934-5909(16)00007-2 | |
| dc.identifier.eissn | 1875-9777 | |
| dc.identifier.uri | ||
| dc.language | eng | |
| dc.publisher | Elsevier BV | |
| dc.relation.ispartof | Cell Stem Cell | |
| dc.relation.isversionof | 10.1016/j.stem.2016.01.006 | |
| dc.subject | Animals | |
| dc.subject | Asymmetric Cell Division | |
| dc.subject | Base Sequence | |
| dc.subject | Cell Differentiation | |
| dc.subject | Cell Lineage | |
| dc.subject | Cell Proliferation | |
| dc.subject | Gene Knockdown Techniques | |
| dc.subject | Inflammation | |
| dc.subject | Membrane Proteins | |
| dc.subject | Mice | |
| dc.subject | MicroRNAs | |
| dc.subject | Molecular Sequence Data | |
| dc.subject | Neoplastic Stem Cells | |
| dc.subject | Nerve Tissue Proteins | |
| dc.subject | Receptors, Notch | |
| dc.subject | Stress, Physiological | |
| dc.subject | Tumor Necrosis Factor-alpha | |
| dc.title | A miR-34a-Numb Feedforward Loop Triggered by Inflammation Regulates Asymmetric Stem Cell Division in Intestine and Colon Cancer. | |
| dc.type | Journal article | |
| duke.contributor.orcid | Shen, Xiling|0000-0002-4978-3531 | |
| pubs.author-url | ||
| pubs.begin-page | 189 | |
| pubs.end-page | 202 | |
| pubs.issue | 2 | |
| pubs.organisational-group | Biomedical Engineering | |
| pubs.organisational-group | Duke | |
| pubs.organisational-group | Duke Cancer Institute | |
| pubs.organisational-group | Institutes and Centers | |
| pubs.organisational-group | Pratt School of Engineering | |
| pubs.organisational-group | School of Medicine | |
| pubs.publication-status | Published | |
| pubs.volume | 18 |
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