TY - JOUR
T1 - Prominin-1 controls stem cell activation by orchestrating ciliary dynamics
AU - Singer, Donald
AU - Thamm, Kristina
AU - Zhuang, Heng
AU - Karbanová, Jana
AU - Gao, Yan
AU - Walker, Jemma Victoria
AU - Jin, Heng
AU - Wu, Xiangnan
AU - Coveney, Clarissa R.
AU - Marangoni, Pauline
AU - Lu, Dongmei
AU - Grayson, Portia Rebecca Clare
AU - Gulsen, Tulay
AU - Liu, Karen J.
AU - Ardu, Stefano
AU - Wann, Angus K.T.
AU - Luo, Shouqing
AU - Zambon, Alexander C.
AU - Jetten, Anton M.
AU - Tredwin, Christopher
AU - Klein, Ophir D.
AU - Attanasio, Massimo
AU - Carmeliet, Peter
AU - Huttner, Wieland B.
AU - Corbeil, Denis
AU - Hu, Bing
N1 - Publisher Copyright:
© 2018 The Authors. Published under the terms of the CC BY 4.0 license
PY - 2019/1/15
Y1 - 2019/1/15
N2 - 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.
AB - 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.
KW - CD133
KW - cilia
KW - sonic hedgehog
KW - stem cells
KW - tooth
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U2 - 10.15252/embj.201899845
DO - 10.15252/embj.201899845
M3 - Article
C2 - 30523147
AN - SCOPUS:85057994651
SN - 0261-4189
VL - 38
JO - EMBO Journal
JF - EMBO Journal
IS - 2
M1 - e99845
ER -