The ets-domain transcription factor Spdef promotes maturation of goblet and paneth cells in the intestinal epithelium.

A. Gregorieff; D.E. Stange; P. Kujala; H.L. Begthel; M.M.W. van den Born; J. Korving; P.J. Peters; H. Clevers

doi:10.1053/j.gastro.2009.06.044

The ets-domain transcription factor Spdef promotes maturation of goblet and paneth cells in the intestinal epithelium.

A. Gregorieff, D.E. Stange, P. Kujala, H.L. Begthel, M.M.W. van den Born, J. Korving, P.J. Peters, H. Clevers

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

192 Citations (Scopus)

Abstract

BACKGROUND & AIMS: Stem cells within the intestinal epithelium generate daughter cells that undergo lineage commitment and maturation through the combined action of the Wnt and Notch signaling cascades. Both pathways, in turn, regulate transcription factor networks that further define differentiation toward either enterocytes or 1 of 3 secretory cell lineages (Paneth, goblet, or enteroendocrine cells). In this study, we investigated the role of the Wnt-responsive, Ets-domain transcription factor Spdef in the differentiation of goblet and Paneth cells. METHODS: The in vivo function of Spdef was examined by disrupting the Spdef gene in mice (Spdef(-/-) mice) and analyzing the intestinal phenotype using a range of histologic techniques and DNA microarray profiling. RESULTS: In accordance with expression data, we found that loss of Spdef severely impaired the maturation of goblet and Paneth cells and, conversely, led to an accumulation of immature secretory progenitors. Spdef appears to positively and negatively regulate a specific subset of goblet and Paneth cell genes, including Cryptdins, Mmp7, Ang4, Kallikreins, and Muc2. CONCLUSIONS: Spdef acts downstream of Math1 to promote terminal differentiation of a secretory progenitor pool into Paneth and goblet cells.

Original language	English
Pages (from-to)	1333-1333
Journal	Gastroenterology
Volume	137
Issue number	4
DOIs	https://doi.org/10.1053/j.gastro.2009.06.044
Publication status	Published - 2009

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title = "The ets-domain transcription factor Spdef promotes maturation of goblet and paneth cells in the intestinal epithelium.",

abstract = "BACKGROUND & AIMS: Stem cells within the intestinal epithelium generate daughter cells that undergo lineage commitment and maturation through the combined action of the Wnt and Notch signaling cascades. Both pathways, in turn, regulate transcription factor networks that further define differentiation toward either enterocytes or 1 of 3 secretory cell lineages (Paneth, goblet, or enteroendocrine cells). In this study, we investigated the role of the Wnt-responsive, Ets-domain transcription factor Spdef in the differentiation of goblet and Paneth cells. METHODS: The in vivo function of Spdef was examined by disrupting the Spdef gene in mice (Spdef(-/-) mice) and analyzing the intestinal phenotype using a range of histologic techniques and DNA microarray profiling. RESULTS: In accordance with expression data, we found that loss of Spdef severely impaired the maturation of goblet and Paneth cells and, conversely, led to an accumulation of immature secretory progenitors. Spdef appears to positively and negatively regulate a specific subset of goblet and Paneth cell genes, including Cryptdins, Mmp7, Ang4, Kallikreins, and Muc2. CONCLUSIONS: Spdef acts downstream of Math1 to promote terminal differentiation of a secretory progenitor pool into Paneth and goblet cells.",

author = "A. Gregorieff and D.E. Stange and P. Kujala and H.L. Begthel and {van den Born}, M.M.W. and J. Korving and P.J. Peters and H. Clevers",

note = "Reporting year: 2009",

year = "2009",

doi = "10.1053/j.gastro.2009.06.044",

language = "English",

volume = "137",

pages = "1333--1333",

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T1 - The ets-domain transcription factor Spdef promotes maturation of goblet and paneth cells in the intestinal epithelium.

AU - Gregorieff, A.

AU - Stange, D.E.

AU - Kujala, P.

AU - Begthel, H.L.

AU - van den Born, M.M.W.

AU - Korving, J.

AU - Peters, P.J.

AU - Clevers, H.

N1 - Reporting year: 2009

PY - 2009

Y1 - 2009

N2 - BACKGROUND & AIMS: Stem cells within the intestinal epithelium generate daughter cells that undergo lineage commitment and maturation through the combined action of the Wnt and Notch signaling cascades. Both pathways, in turn, regulate transcription factor networks that further define differentiation toward either enterocytes or 1 of 3 secretory cell lineages (Paneth, goblet, or enteroendocrine cells). In this study, we investigated the role of the Wnt-responsive, Ets-domain transcription factor Spdef in the differentiation of goblet and Paneth cells. METHODS: The in vivo function of Spdef was examined by disrupting the Spdef gene in mice (Spdef(-/-) mice) and analyzing the intestinal phenotype using a range of histologic techniques and DNA microarray profiling. RESULTS: In accordance with expression data, we found that loss of Spdef severely impaired the maturation of goblet and Paneth cells and, conversely, led to an accumulation of immature secretory progenitors. Spdef appears to positively and negatively regulate a specific subset of goblet and Paneth cell genes, including Cryptdins, Mmp7, Ang4, Kallikreins, and Muc2. CONCLUSIONS: Spdef acts downstream of Math1 to promote terminal differentiation of a secretory progenitor pool into Paneth and goblet cells.

AB - BACKGROUND & AIMS: Stem cells within the intestinal epithelium generate daughter cells that undergo lineage commitment and maturation through the combined action of the Wnt and Notch signaling cascades. Both pathways, in turn, regulate transcription factor networks that further define differentiation toward either enterocytes or 1 of 3 secretory cell lineages (Paneth, goblet, or enteroendocrine cells). In this study, we investigated the role of the Wnt-responsive, Ets-domain transcription factor Spdef in the differentiation of goblet and Paneth cells. METHODS: The in vivo function of Spdef was examined by disrupting the Spdef gene in mice (Spdef(-/-) mice) and analyzing the intestinal phenotype using a range of histologic techniques and DNA microarray profiling. RESULTS: In accordance with expression data, we found that loss of Spdef severely impaired the maturation of goblet and Paneth cells and, conversely, led to an accumulation of immature secretory progenitors. Spdef appears to positively and negatively regulate a specific subset of goblet and Paneth cell genes, including Cryptdins, Mmp7, Ang4, Kallikreins, and Muc2. CONCLUSIONS: Spdef acts downstream of Math1 to promote terminal differentiation of a secretory progenitor pool into Paneth and goblet cells.

U2 - 10.1053/j.gastro.2009.06.044

DO - 10.1053/j.gastro.2009.06.044

M3 - Article

SN - 0016-5085

VL - 137

SP - 1333

EP - 1333

JO - Gastroenterology

JF - Gastroenterology

IS - 4

ER -

The ets-domain transcription factor Spdef promotes maturation of goblet and paneth cells in the intestinal epithelium.

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