SATB2 preserves colon stem cell identity and mediates ileum-colon conversion via enhancer remodeling

Wei Gu; Hua Wang; Xiaofeng Huang; Judith Kraiczy; Pratik N.P. Singh; Charles Ng; Sezin Dagdeviren; Sean Houghton; Oscar Pellon-Cardenas; Ying Lan; Yaohui Nie; Jiaoyue Zhang; Kushal K. Banerjee; Emily J. Onufer; Brad W. Warner; Jason Spence; Ellen Scherl; Shahin Rafii; Richard T. Lee; Michael P. Verzi; David Redmond; Randy Longman; Kristian Helin; Ramesh A. Shivdasani; Qiao Zhou

doi:10.1016/j.stem.2021.09.004

SATB2 preserves colon stem cell identity and mediates ileum-colon conversion via enhancer remodeling

Wei Gu, Hua Wang, Xiaofeng Huang, Judith Kraiczy, Pratik N.P. Singh, Charles Ng, Sezin Dagdeviren, Sean Houghton, Oscar Pellon-Cardenas, Ying Lan, Yaohui Nie, Jiaoyue Zhang, Kushal K. Banerjee, Emily J. Onufer, Brad W. Warner, Jason Spence, Ellen Scherl, Shahin Rafii, Richard T. Lee, Michael P. VerziDavid Redmond, Randy Longman, Kristian Helin, Ramesh A. Shivdasani, Qiao Zhou

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

30 Scopus citations

Abstract

Adult stem cells maintain regenerative tissue structure and function by producing tissue-specific progeny, but the factors that preserve their tissue identities are not well understood. The small and large intestines differ markedly in cell composition and function, reflecting their distinct stem cell populations. Here we show that SATB2, a colon-restricted chromatin factor, singularly preserves LGR5⁺ adult colonic stem cell and epithelial identity in mice and humans. Satb2 loss in adult mice leads to stable conversion of colonic stem cells into small intestine ileal-like stem cells and replacement of the colonic mucosa with one that resembles the ileum. Conversely, SATB2 confers colonic properties on the mouse ileum. Human colonic organoids also adopt ileal characteristics upon SATB2 loss. SATB2 regulates colonic identity in part by modulating enhancer binding of the intestinal transcription factors CDX2 and HNF4A. Our study uncovers a conserved core regulator of colonic stem cells able to mediate cross-tissue plasticity in mature intestines.

Original language	English
Pages (from-to)	101-115.e10
Journal	Cell Stem Cell
Volume	29
Issue number	1
DOIs	https://doi.org/10.1016/j.stem.2021.09.004
State	Published - Jan 6 2022

Keywords

SATB2, intestine regeneration, colonic mucosa, stem cell conversion, enhancer remodelingintestine

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10.1016/j.stem.2021.09.004

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Gu, W., Wang, H., Huang, X., Kraiczy, J., Singh, P. N. P., Ng, C., Dagdeviren, S., Houghton, S., Pellon-Cardenas, O., Lan, Y., Nie, Y., Zhang, J., Banerjee, K. K., Onufer, E. J., Warner, B. W., Spence, J., Scherl, E., Rafii, S., Lee, R. T., ... Zhou, Q. (2022). SATB2 preserves colon stem cell identity and mediates ileum-colon conversion via enhancer remodeling. Cell Stem Cell, 29(1), 101-115.e10. https://doi.org/10.1016/j.stem.2021.09.004

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title = "SATB2 preserves colon stem cell identity and mediates ileum-colon conversion via enhancer remodeling",

abstract = "Adult stem cells maintain regenerative tissue structure and function by producing tissue-specific progeny, but the factors that preserve their tissue identities are not well understood. The small and large intestines differ markedly in cell composition and function, reflecting their distinct stem cell populations. Here we show that SATB2, a colon-restricted chromatin factor, singularly preserves LGR5+ adult colonic stem cell and epithelial identity in mice and humans. Satb2 loss in adult mice leads to stable conversion of colonic stem cells into small intestine ileal-like stem cells and replacement of the colonic mucosa with one that resembles the ileum. Conversely, SATB2 confers colonic properties on the mouse ileum. Human colonic organoids also adopt ileal characteristics upon SATB2 loss. SATB2 regulates colonic identity in part by modulating enhancer binding of the intestinal transcription factors CDX2 and HNF4A. Our study uncovers a conserved core regulator of colonic stem cells able to mediate cross-tissue plasticity in mature intestines.",

keywords = "SATB2, intestine regeneration, colonic mucosa, stem cell conversion, enhancer remodelingintestine",

author = "Wei Gu and Hua Wang and Xiaofeng Huang and Judith Kraiczy and Singh, {Pratik N.P.} and Charles Ng and Sezin Dagdeviren and Sean Houghton and Oscar Pellon-Cardenas and Ying Lan and Yaohui Nie and Jiaoyue Zhang and Banerjee, {Kushal K.} and Onufer, {Emily J.} and Warner, {Brad W.} and Jason Spence and Ellen Scherl and Shahin Rafii and Lee, {Richard T.} and Verzi, {Michael P.} and David Redmond and Randy Longman and Kristian Helin and Shivdasani, {Ramesh A.} and Qiao Zhou",

note = "Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",

year = "2022",

month = jan,

day = "6",

doi = "10.1016/j.stem.2021.09.004",

language = "English",

volume = "29",

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journal = "Cell Stem Cell",

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Gu, W, Wang, H, Huang, X, Kraiczy, J, Singh, PNP, Ng, C, Dagdeviren, S, Houghton, S, Pellon-Cardenas, O, Lan, Y, Nie, Y, Zhang, J, Banerjee, KK, Onufer, EJ, Warner, BW, Spence, J, Scherl, E, Rafii, S, Lee, RT, Verzi, MP, Redmond, D, Longman, R, Helin, K, Shivdasani, RA & Zhou, Q 2022, 'SATB2 preserves colon stem cell identity and mediates ileum-colon conversion via enhancer remodeling', Cell Stem Cell, vol. 29, no. 1, pp. 101-115.e10. https://doi.org/10.1016/j.stem.2021.09.004

TY - JOUR

T1 - SATB2 preserves colon stem cell identity and mediates ileum-colon conversion via enhancer remodeling

AU - Gu, Wei

AU - Wang, Hua

AU - Huang, Xiaofeng

AU - Kraiczy, Judith

AU - Singh, Pratik N.P.

AU - Ng, Charles

AU - Dagdeviren, Sezin

AU - Houghton, Sean

AU - Pellon-Cardenas, Oscar

AU - Lan, Ying

AU - Nie, Yaohui

AU - Zhang, Jiaoyue

AU - Banerjee, Kushal K.

AU - Onufer, Emily J.

AU - Warner, Brad W.

AU - Spence, Jason

AU - Scherl, Ellen

AU - Rafii, Shahin

AU - Lee, Richard T.

AU - Verzi, Michael P.

AU - Redmond, David

AU - Longman, Randy

AU - Helin, Kristian

AU - Shivdasani, Ramesh A.

AU - Zhou, Qiao

PY - 2022/1/6

Y1 - 2022/1/6

N2 - Adult stem cells maintain regenerative tissue structure and function by producing tissue-specific progeny, but the factors that preserve their tissue identities are not well understood. The small and large intestines differ markedly in cell composition and function, reflecting their distinct stem cell populations. Here we show that SATB2, a colon-restricted chromatin factor, singularly preserves LGR5+ adult colonic stem cell and epithelial identity in mice and humans. Satb2 loss in adult mice leads to stable conversion of colonic stem cells into small intestine ileal-like stem cells and replacement of the colonic mucosa with one that resembles the ileum. Conversely, SATB2 confers colonic properties on the mouse ileum. Human colonic organoids also adopt ileal characteristics upon SATB2 loss. SATB2 regulates colonic identity in part by modulating enhancer binding of the intestinal transcription factors CDX2 and HNF4A. Our study uncovers a conserved core regulator of colonic stem cells able to mediate cross-tissue plasticity in mature intestines.

AB - Adult stem cells maintain regenerative tissue structure and function by producing tissue-specific progeny, but the factors that preserve their tissue identities are not well understood. The small and large intestines differ markedly in cell composition and function, reflecting their distinct stem cell populations. Here we show that SATB2, a colon-restricted chromatin factor, singularly preserves LGR5+ adult colonic stem cell and epithelial identity in mice and humans. Satb2 loss in adult mice leads to stable conversion of colonic stem cells into small intestine ileal-like stem cells and replacement of the colonic mucosa with one that resembles the ileum. Conversely, SATB2 confers colonic properties on the mouse ileum. Human colonic organoids also adopt ileal characteristics upon SATB2 loss. SATB2 regulates colonic identity in part by modulating enhancer binding of the intestinal transcription factors CDX2 and HNF4A. Our study uncovers a conserved core regulator of colonic stem cells able to mediate cross-tissue plasticity in mature intestines.

KW - SATB2, intestine regeneration, colonic mucosa, stem cell conversion, enhancer remodelingintestine

UR - http://www.scopus.com/inward/record.url?scp=85121988081&partnerID=8YFLogxK

U2 - 10.1016/j.stem.2021.09.004

DO - 10.1016/j.stem.2021.09.004

M3 - Article

C2 - 34582804

AN - SCOPUS:85121988081

SN - 1934-5909

VL - 29

SP - 101-115.e10

JO - Cell Stem Cell

JF - Cell Stem Cell

IS - 1

ER -

SATB2 preserves colon stem cell identity and mediates ileum-colon conversion via enhancer remodeling

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Keywords

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