HMGA1 amplifies Wnt signalling and expands the intestinal stem cell compartment and Paneth cell niche

Lingling Xian; Dan Georgess; Tait Huso; Leslie Cope; Amy Belton; Yu Ting Chang; Wenyong Kuang; Qihua Gu; Xiaoyan Zhang; Stefania Senger; Alessio Fasano; David L. Huso; Andrew J. Ewald; Linda M.S. Resar

doi:10.1038/ncomms15008

HMGA1 amplifies Wnt signalling and expands the intestinal stem cell compartment and Paneth cell niche

Lingling Xian, Dan Georgess, Tait Huso, Leslie Cope, Amy Belton, Yu Ting Chang, Wenyong Kuang, Qihua Gu, Xiaoyan Zhang, Stefania Senger, Alessio Fasano, David L. Huso, Andrew J. Ewald, Linda M.S. Resar

School of Medicine

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

32 Scopus citations

Abstract

High-mobility group A1 (Hmga1) chromatin remodelling proteins are enriched in intestinal stem cells (ISCs), although their function in this setting was unknown. Prior studies showed that Hmga1 drives hyperproliferation, aberrant crypt formation and polyposis in transgenic mice. Here we demonstrate that Hmga1 amplifies Wnt/β-catenin signalling to enhance selfrenewal and expand the ISC compartment. Hmga1 upregulates genes encoding both Wnt agonist receptors and downstream Wnt effectors. Hmga1 also helps to 'build' an ISC niche by expanding the Paneth cell compartment and directly inducing Sox9, which is required for Paneth cell differentiation. In human intestine, HMGA1 and SOX9 are positively correlated, and both become upregulated in colorectal cancer. Our results define a unique role for Hmga1 in intestinal homeostasis by maintaining the stem cell pool and fostering terminal differentiation to establish an epithelial stem cell niche. This work also suggests that deregulated Hmga1 perturbs this equilibrium during intestinal carcinogenesis.

Original language	English (US)
Article number	15008
Journal	Nature communications
Volume	8
DOIs	https://doi.org/10.1038/ncomms15008
State	Published - 2017

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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10.1038/ncomms15008

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title = "HMGA1 amplifies Wnt signalling and expands the intestinal stem cell compartment and Paneth cell niche",

abstract = "High-mobility group A1 (Hmga1) chromatin remodelling proteins are enriched in intestinal stem cells (ISCs), although their function in this setting was unknown. Prior studies showed that Hmga1 drives hyperproliferation, aberrant crypt formation and polyposis in transgenic mice. Here we demonstrate that Hmga1 amplifies Wnt/β-catenin signalling to enhance selfrenewal and expand the ISC compartment. Hmga1 upregulates genes encoding both Wnt agonist receptors and downstream Wnt effectors. Hmga1 also helps to 'build' an ISC niche by expanding the Paneth cell compartment and directly inducing Sox9, which is required for Paneth cell differentiation. In human intestine, HMGA1 and SOX9 are positively correlated, and both become upregulated in colorectal cancer. Our results define a unique role for Hmga1 in intestinal homeostasis by maintaining the stem cell pool and fostering terminal differentiation to establish an epithelial stem cell niche. This work also suggests that deregulated Hmga1 perturbs this equilibrium during intestinal carcinogenesis.",

author = "Lingling Xian and Dan Georgess and Tait Huso and Leslie Cope and Amy Belton and Chang, {Yu Ting} and Wenyong Kuang and Qihua Gu and Xiaoyan Zhang and Stefania Senger and Alessio Fasano and Huso, {David L.} and Ewald, {Andrew J.} and Resar, {Linda M.S.}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2017.",

year = "2017",

doi = "10.1038/ncomms15008",

language = "English (US)",

volume = "8",

journal = "Nature communications",

issn = "2041-1723",

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T1 - HMGA1 amplifies Wnt signalling and expands the intestinal stem cell compartment and Paneth cell niche

AU - Xian, Lingling

AU - Georgess, Dan

AU - Huso, Tait

AU - Cope, Leslie

AU - Belton, Amy

AU - Chang, Yu Ting

AU - Kuang, Wenyong

AU - Gu, Qihua

AU - Zhang, Xiaoyan

AU - Senger, Stefania

AU - Fasano, Alessio

AU - Huso, David L.

AU - Ewald, Andrew J.

AU - Resar, Linda M.S.

PY - 2017

Y1 - 2017

N2 - High-mobility group A1 (Hmga1) chromatin remodelling proteins are enriched in intestinal stem cells (ISCs), although their function in this setting was unknown. Prior studies showed that Hmga1 drives hyperproliferation, aberrant crypt formation and polyposis in transgenic mice. Here we demonstrate that Hmga1 amplifies Wnt/β-catenin signalling to enhance selfrenewal and expand the ISC compartment. Hmga1 upregulates genes encoding both Wnt agonist receptors and downstream Wnt effectors. Hmga1 also helps to 'build' an ISC niche by expanding the Paneth cell compartment and directly inducing Sox9, which is required for Paneth cell differentiation. In human intestine, HMGA1 and SOX9 are positively correlated, and both become upregulated in colorectal cancer. Our results define a unique role for Hmga1 in intestinal homeostasis by maintaining the stem cell pool and fostering terminal differentiation to establish an epithelial stem cell niche. This work also suggests that deregulated Hmga1 perturbs this equilibrium during intestinal carcinogenesis.

AB - High-mobility group A1 (Hmga1) chromatin remodelling proteins are enriched in intestinal stem cells (ISCs), although their function in this setting was unknown. Prior studies showed that Hmga1 drives hyperproliferation, aberrant crypt formation and polyposis in transgenic mice. Here we demonstrate that Hmga1 amplifies Wnt/β-catenin signalling to enhance selfrenewal and expand the ISC compartment. Hmga1 upregulates genes encoding both Wnt agonist receptors and downstream Wnt effectors. Hmga1 also helps to 'build' an ISC niche by expanding the Paneth cell compartment and directly inducing Sox9, which is required for Paneth cell differentiation. In human intestine, HMGA1 and SOX9 are positively correlated, and both become upregulated in colorectal cancer. Our results define a unique role for Hmga1 in intestinal homeostasis by maintaining the stem cell pool and fostering terminal differentiation to establish an epithelial stem cell niche. This work also suggests that deregulated Hmga1 perturbs this equilibrium during intestinal carcinogenesis.

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HMGA1 amplifies Wnt signalling and expands the intestinal stem cell compartment and Paneth cell niche

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ASJC Scopus subject areas

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