Journal
EMBO JOURNAL
Volume 38, Issue 2, Pages -Publisher
WILEY
DOI: 10.15252/embj.201899845
Keywords
CD133; cilia; sonic hedgehog; stem cells; tooth
Categories
Funding
- National Institutes of Health [R01DK090326-01A1, R35-DE026602]
- National Natural Science Foundation of China [30801289, 81371138]
- Arthritis Research United Kingdom (ARUK) Centre for Osteoarthritis Pathogenesis Grant [20205, 21621]
- VIB TechWatch program
- Flemish Government
- Research Foundation Flanders (FWO-Vlaanderen)
- Foundation against Cancer [2016-078]
- Kom op Tegen Kanker (Stand up to Cancer, Flemish Cancer Society)
- ERC Advanced Research Grant [EU-ERC743074]
- Deutsche Forschungsgemeinschaft (DFG) [SFB 655]
- European Union Marie Sklodowska-Curie actions [618930]
- European Regional Development Fund
- Biotechnology and Biological Sciences Research Council of the UK [BB/L02392X/1]
- KTRR Prize studentship
- BBSRC [BB/E013872/1, BB/L02392X/1] Funding Source: UKRI
- MRC [MR/M023605/1] Funding Source: UKRI
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [ZIAES100485] Funding Source: NIH RePORTER
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Proper temporal and spatial activation of stem cells relies on highly coordinated cell signaling. The primary cilium is the sensory organelle that is responsible for transmitting extracellular signals into a cell. Primary cilium size, architecture, and assembly-disassembly dynamics are under rigid cell cycle-dependent control. Using mouse incisor tooth epithelia as a model, we show that ciliary dynamics in stem cells require the proper functions of a cholesterol-binding membrane glycoprotein, Prominin-1 (Prom1/CD133), which controls sequential recruitment of ciliary membrane components, histone deacetylase, and transcription factors. Nuclear translocation of Prom1 and these molecules is particularly evident in transit amplifying cells, the immediate derivatives of stem cells. The absence of Prom1 impairs ciliary dynamics and abolishes the growth stimulation effects of sonic hedgehog (SHH) treatment, resulting in the disruption of stem cell quiescence maintenance and activation. We propose that Prom1 is a key regulator ensuring appropriate response of stem cells to extracellular signals, with important implications for development, regeneration, and diseases.
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