ERM is required for transcriptional control of the spermatogonial stem cell niche

Chen Chen; Wenjun Ouyang; Vadim Grigura; Qing Zhou; Kay Carnes; Hyunjung Lim; Guang Quan Zhao; Silvia Arber; Natasza Kurpios; Theresa L. Murphy; Alec M. Cheng; John A. Hassell; Varadaraj Chandrashekar; Marie Claude Hofmann; Rex A. Hess; Kenneth M. Murphy

doi:10.1038/nature03894

ERM is required for transcriptional control of the spermatogonial stem cell niche

Chen Chen, Wenjun Ouyang, Vadim Grigura, Qing Zhou, Kay Carnes, Hyunjung Lim, Guang Quan Zhao, Silvia Arber, Natasza Kurpios, Theresa L. Murphy, Alec M. Cheng, John A. Hassell, Varadaraj Chandrashekar, Marie Claude Hofmann, Rex A. Hess, Kenneth M. Murphy

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284 Scopus citations

Abstract

Division of spermatogonial stem cells produces daughter cells that either maintain their stem cell identity or undergo differentiation to form mature sperm. The Sertoli cell, the only somatic cell within seminiferous tubules, provides the stem cell niche through physical support and expression of surface proteins and soluble factors. Here we show that the Ets related molecule (ERM) is expressed exclusively within Sertoli cells in the testis and is required for spermatogonial stem cell self-renewal. Mice with targeted disruption of ERM have a loss of maintenance of spermatogonial stem cell self-renewal without a block in normal spermatogenic differentiation and thus have progressive germ-cell depletion and a Sertoli-cell-only syndrome. Microarray analysis of primary Sertoli cells from ERM-deficient mice showed alterations in secreted factors known to regulate the haematopoietic stem cell niche. These results identify a new function for the Ets family transcription factors in spermatogenesis and provide an example of transcriptional control of a vertebrate stem cell niche.

Original language	English
Pages (from-to)	1030-1034
Number of pages	5
Journal	Nature
Volume	436
Issue number	7053
DOIs	https://doi.org/10.1038/nature03894
State	Published - Aug 18 2005

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@article{e557cbac6f934ba68677bf676f298b61,

title = "ERM is required for transcriptional control of the spermatogonial stem cell niche",

abstract = "Division of spermatogonial stem cells produces daughter cells that either maintain their stem cell identity or undergo differentiation to form mature sperm. The Sertoli cell, the only somatic cell within seminiferous tubules, provides the stem cell niche through physical support and expression of surface proteins and soluble factors. Here we show that the Ets related molecule (ERM) is expressed exclusively within Sertoli cells in the testis and is required for spermatogonial stem cell self-renewal. Mice with targeted disruption of ERM have a loss of maintenance of spermatogonial stem cell self-renewal without a block in normal spermatogenic differentiation and thus have progressive germ-cell depletion and a Sertoli-cell-only syndrome. Microarray analysis of primary Sertoli cells from ERM-deficient mice showed alterations in secreted factors known to regulate the haematopoietic stem cell niche. These results identify a new function for the Ets family transcription factors in spermatogenesis and provide an example of transcriptional control of a vertebrate stem cell niche.",

author = "Chen Chen and Wenjun Ouyang and Vadim Grigura and Qing Zhou and Kay Carnes and Hyunjung Lim and Zhao, {Guang Quan} and Silvia Arber and Natasza Kurpios and Murphy, {Theresa L.} and Cheng, {Alec M.} and Hassell, {John A.} and Varadaraj Chandrashekar and Hofmann, {Marie Claude} and Hess, {Rex A.} and Murphy, {Kenneth M.}",

note = "Funding Information: Acknowledgements We thank M. White for blastocyst microinjections; X. Cheng for helpful discussion; B. Sleckman for targeting vector; D. Ornitz, M. Griswold and K. Sheehan for reagents and antibody production; and T. Jessell for help with ERMIRES-LacZmice. J.A.H. acknowledges funding from the Canadian Breast Cancer Research Alliance, the Canadian Institutes of Health Research and the DOD Breast Cancer Research Program. N.A.K. was supported by a DOD Breast Cancer Research Program Scholarship. K.M.M. is an investigator of the Howard Hughes Medical Institute.",

year = "2005",

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doi = "10.1038/nature03894",

language = "English",

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journal = "Nature",

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T1 - ERM is required for transcriptional control of the spermatogonial stem cell niche

AU - Chen, Chen

AU - Ouyang, Wenjun

AU - Grigura, Vadim

AU - Zhou, Qing

AU - Carnes, Kay

AU - Lim, Hyunjung

AU - Zhao, Guang Quan

AU - Arber, Silvia

AU - Kurpios, Natasza

AU - Murphy, Theresa L.

AU - Cheng, Alec M.

AU - Hassell, John A.

AU - Chandrashekar, Varadaraj

AU - Hofmann, Marie Claude

AU - Hess, Rex A.

AU - Murphy, Kenneth M.

N1 - Funding Information: Acknowledgements We thank M. White for blastocyst microinjections; X. Cheng for helpful discussion; B. Sleckman for targeting vector; D. Ornitz, M. Griswold and K. Sheehan for reagents and antibody production; and T. Jessell for help with ERMIRES-LacZmice. J.A.H. acknowledges funding from the Canadian Breast Cancer Research Alliance, the Canadian Institutes of Health Research and the DOD Breast Cancer Research Program. N.A.K. was supported by a DOD Breast Cancer Research Program Scholarship. K.M.M. is an investigator of the Howard Hughes Medical Institute.

PY - 2005/8/18

Y1 - 2005/8/18

N2 - Division of spermatogonial stem cells produces daughter cells that either maintain their stem cell identity or undergo differentiation to form mature sperm. The Sertoli cell, the only somatic cell within seminiferous tubules, provides the stem cell niche through physical support and expression of surface proteins and soluble factors. Here we show that the Ets related molecule (ERM) is expressed exclusively within Sertoli cells in the testis and is required for spermatogonial stem cell self-renewal. Mice with targeted disruption of ERM have a loss of maintenance of spermatogonial stem cell self-renewal without a block in normal spermatogenic differentiation and thus have progressive germ-cell depletion and a Sertoli-cell-only syndrome. Microarray analysis of primary Sertoli cells from ERM-deficient mice showed alterations in secreted factors known to regulate the haematopoietic stem cell niche. These results identify a new function for the Ets family transcription factors in spermatogenesis and provide an example of transcriptional control of a vertebrate stem cell niche.

AB - Division of spermatogonial stem cells produces daughter cells that either maintain their stem cell identity or undergo differentiation to form mature sperm. The Sertoli cell, the only somatic cell within seminiferous tubules, provides the stem cell niche through physical support and expression of surface proteins and soluble factors. Here we show that the Ets related molecule (ERM) is expressed exclusively within Sertoli cells in the testis and is required for spermatogonial stem cell self-renewal. Mice with targeted disruption of ERM have a loss of maintenance of spermatogonial stem cell self-renewal without a block in normal spermatogenic differentiation and thus have progressive germ-cell depletion and a Sertoli-cell-only syndrome. Microarray analysis of primary Sertoli cells from ERM-deficient mice showed alterations in secreted factors known to regulate the haematopoietic stem cell niche. These results identify a new function for the Ets family transcription factors in spermatogenesis and provide an example of transcriptional control of a vertebrate stem cell niche.

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JO - Nature

JF - Nature

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ER -

ERM is required for transcriptional control of the spermatogonial stem cell niche

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