PMID- 19549527
OWN - NLM
STAT- MEDLINE
DCOM- 20091015
LR  - 20151119
IS  - 1528-0012 (Electronic)
IS  - 0016-5085 (Linking)
VI  - 137
IP  - 4
DP  - 2009 Oct
TI  - The ets-domain transcription factor Spdef promotes maturation of goblet and 
      paneth cells in the intestinal epithelium.
PG  - 1333-45.e1-3
LID - 10.1053/j.gastro.2009.06.044 [doi]
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.
FAU - Gregorieff, Alex
AU  - Gregorieff A
AD  - Hubrecht Institute, Utrecht, The Netherlands.
FAU - Stange, Daniel E
AU  - Stange DE
FAU - Kujala, Pekka
AU  - Kujala P
FAU - Begthel, Harry
AU  - Begthel H
FAU - van den Born, Maaike
AU  - van den Born M
FAU - Korving, Jeroen
AU  - Korving J
FAU - Peters, Peter J
AU  - Peters PJ
FAU - Clevers, Hans
AU  - Clevers H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090621
PL  - United States
TA  - Gastroenterology
JT  - Gastroenterology
JID - 0374630
RN  - 0 (Biomarkers)
RN  - 0 (Proto-Oncogene Proteins c-ets)
RN  - 0 (Spdef protein, mouse)
SB  - IM
MH  - Animals
MH  - Biomarkers/metabolism
MH  - *Cell Differentiation/genetics
MH  - Cell Lineage
MH  - Colon/*metabolism/ultrastructure
MH  - Gene Expression Profiling/methods
MH  - Gene Expression Regulation
MH  - Genotype
MH  - Goblet Cells/*metabolism/ultrastructure
MH  - Intestine, Small/*metabolism/ultrastructure
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Oligonucleotide Array Sequence Analysis
MH  - Paneth Cells/*metabolism/ultrastructure
MH  - Phenotype
MH  - Proto-Oncogene Proteins c-ets/deficiency/genetics/*metabolism
MH  - Stem Cells/*metabolism/ultrastructure
MH  - Transcription, Genetic
EDAT- 2009/06/25 09:00
MHDA- 2009/10/16 06:00
CRDT- 2009/06/25 09:00
PHST- 2009/02/21 00:00 [received]
PHST- 2009/06/02 00:00 [revised]
PHST- 2009/06/10 00:00 [accepted]
PHST- 2009/06/25 09:00 [entrez]
PHST- 2009/06/25 09:00 [pubmed]
PHST- 2009/10/16 06:00 [medline]
AID - S0016-5085(09)01001-4 [pii]
AID - 10.1053/j.gastro.2009.06.044 [doi]
PST - ppublish
SO  - Gastroenterology. 2009 Oct;137(4):1333-45.e1-3. doi: 
      10.1053/j.gastro.2009.06.044. Epub 2009 Jun 21.