Prominin-1 controls stem cell activation by orchestrating ciliary dynamics

Donald Singer; Kristina Thamm; Heng Zhuang; Jana Karbanová; Yan Gao; Jemma Victoria Walker; Heng Jin; Xiangnan Wu; Clarissa R. Coveney; Pauline Marangoni; Dongmei Lu; Portia Rebecca Clare Grayson; Tulay Gulsen; Karen J. Liu; Stefano Ardu; Angus K.T. Wann; Shouqing Luo; Alexander C. Zambon; Anton M. Jetten; Christopher Tredwin; Ophir D. Klein; Massimo Attanasio; Peter Carmeliet; Wieland B. Huttner; Denis Corbeil; Bing Hu

doi:10.15252/embj.201899845

Prominin-1 controls stem cell activation by orchestrating ciliary dynamics

Donald Singer
, Kristina Thamm
, Heng Zhuang
, Jana Karbanová
, Yan Gao
, Jemma Victoria Walker
, Heng Jin
, Xiangnan Wu
, Clarissa R. Coveney
, Pauline Marangoni
, Dongmei Lu
, Portia Rebecca Clare Grayson
, Tulay Gulsen
, Karen J. Liu
, Stefano Ardu
, Angus K.T. Wann
, Shouqing Luo
, Alexander C. Zambon
, Anton M. Jetten
, Christopher Tredwin

Ophir D. Klein, Massimo Attanasio, Peter Carmeliet, Wieland B. Huttner, Denis Corbeil^*, Bing Hu

^*Corresponding author for this work

University of Plymouth
TU Dresden
Peking University
Capital Medical University
University of Iowa
Tianjin Medical University
University of California, San Francisco
University of Oxford
Medical Center
UCL University College London
Centre for Craniofacial and Regenerative Biology
Global Health Institute
Keck Graduate Institute
NIEHS - National Institute of Environmental Health Sciences (NIH)
KU Leuven
Max Planck Institute of Molecular Cell Biology and Genetics

Research output: Contribution to journal › Article › peer-review

57 Citations (Scopus)

312 Downloads (Pure)

Abstract

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.

Original language	English
Article number	e99845
Journal	The EMBO journal
Volume	38
Issue number	2
Early online date	6 Dec 2018
DOIs	https://doi.org/10.15252/embj.201899845
Publication status	Published - 15 Jan 2019

Keywords

CD133
cilia
sonic hedgehog
stem cells
tooth

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10.15252/embj.201899845Licence: CC BY

Prominin-1 controls stem cell_SINGER_Accepted18 October 2018_GOLD VoR(CC BY)Final published version, 5.29 MBLicence: CC BY

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Singer, D., Thamm, K., Zhuang, H., Karbanová, J., Gao, Y., Walker, J. V., Jin, H., Wu, X., Coveney, C. R., Marangoni, P., Lu, D., Grayson, P. R. C., Gulsen, T., Liu, K. J., Ardu, S., Wann, A. K. T., Luo, S., Zambon, A. C., Jetten, A. M., ... Hu, B. (2019). Prominin-1 controls stem cell activation by orchestrating ciliary dynamics. The EMBO journal, 38(2), Article e99845. https://doi.org/10.15252/embj.201899845

@article{b7fe53aa359048cf88dcc9d83b125096,

title = "Prominin-1 controls stem cell activation by orchestrating ciliary dynamics",

abstract = "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.",

keywords = "CD133, cilia, sonic hedgehog, stem cells, tooth",

author = "Donald Singer and Kristina Thamm and Heng Zhuang and Jana Karbanov{\'a} and Yan Gao and Walker, \{Jemma Victoria\} and Heng Jin and Xiangnan Wu and Coveney, \{Clarissa R.\} and Pauline Marangoni and Dongmei Lu and Grayson, \{Portia Rebecca Clare\} and Tulay Gulsen and Liu, \{Karen J.\} and Stefano Ardu and Wann, \{Angus K.T.\} and Shouqing Luo and Zambon, \{Alexander C.\} and Jetten, \{Anton M.\} and Christopher Tredwin and Klein, \{Ophir D.\} and Massimo Attanasio and Peter Carmeliet and Huttner, \{Wieland B.\} and Denis Corbeil and Bing Hu",

year = "2019",

month = jan,

day = "15",

doi = "10.15252/embj.201899845",

language = "English",

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journal = "The EMBO journal",

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Singer, D, Thamm, K, Zhuang, H, Karbanová, J, Gao, Y, Walker, JV, Jin, H, Wu, X, Coveney, CR, Marangoni, P, Lu, D, Grayson, PRC, Gulsen, T, Liu, KJ, Ardu, S, Wann, AKT, Luo, S, Zambon, AC, Jetten, AM, Tredwin, C, Klein, OD, Attanasio, M, Carmeliet, P, Huttner, WB, Corbeil, D & Hu, B 2019, 'Prominin-1 controls stem cell activation by orchestrating ciliary dynamics', The EMBO journal, vol. 38, no. 2, e99845. https://doi.org/10.15252/embj.201899845

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

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

UR - https://www.scopus.com/pages/publications/85057994651

U2 - 10.15252/embj.201899845

DO - 10.15252/embj.201899845

M3 - Article

C2 - 30523147

AN - SCOPUS:85057994651

SN - 0261-4189

VL - 38

JO - The EMBO journal

JF - The EMBO journal

IS - 2

M1 - e99845

ER -

Prominin-1 controls stem cell activation by orchestrating ciliary dynamics

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Keywords

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