PMID- 22190634
OWN - NLM
STAT- MEDLINE
DCOM- 20120306
LR  - 20220316
IS  - 1477-9129 (Electronic)
IS  - 0950-1991 (Print)
IS  - 0950-1991 (Linking)
VI  - 139
IP  - 3
DP  - 2012 Feb
TI  - Notch signaling modulates proliferation and differentiation of intestinal crypt 
      base columnar stem cells.
PG  - 488-97
LID - 10.1242/dev.070763 [doi]
AB  - Notch signaling is known to regulate the proliferation and differentiation of 
      intestinal stem and progenitor cells; however, direct cellular targets and 
      specific functions of Notch signals had not been identified. We show here in mice 
      that Notch directly targets the crypt base columnar (CBC) cell to maintain stem 
      cell activity. Notch inhibition induced rapid CBC cell loss, with reduced 
      proliferation, apoptotic cell death and reduced efficiency of organoid 
      initiation. Furthermore, expression of the CBC stem cell-specific marker Olfm4 
      was directly dependent on Notch signaling, with transcription activated through 
      RBP-Jkappa binding sites in the promoter. Notch inhibition also led to precocious 
      differentiation of epithelial progenitors into secretory cell types, including 
      large numbers of cells that expressed both Paneth and goblet cell markers. 
      Analysis of Notch function in Atoh1-deficient intestine demonstrated that the 
      cellular changes were dependent on Atoh1, whereas Notch regulation of Olfm4 gene 
      expression was Atoh1 independent. Our findings suggest that Notch targets 
      distinct progenitor cell populations to maintain adult intestinal stem cells and 
      to regulate cell fate choice to control epithelial cell homeostasis.
FAU - VanDussen, Kelli L
AU  - VanDussen KL
AD  - Department of Molecular & Integrative Physiology, The University of Michigan, Ann 
      Arbor, MI 48109, USA.
FAU - Carulli, Alexis J
AU  - Carulli AJ
FAU - Keeley, Theresa M
AU  - Keeley TM
FAU - Patel, Sanjeevkumar R
AU  - Patel SR
FAU - Puthoff, Brent J
AU  - Puthoff BJ
FAU - Magness, Scott T
AU  - Magness ST
FAU - Tran, Ivy T
AU  - Tran IT
FAU - Maillard, Ivan
AU  - Maillard I
FAU - Siebel, Christian
AU  - Siebel C
FAU - Kolterud, Asa
AU  - Kolterud A
FAU - Grosse, Ann S
AU  - Grosse AS
FAU - Gumucio, Deborah L
AU  - Gumucio DL
FAU - Ernst, Stephen A
AU  - Ernst SA
FAU - Tsai, Yu-Hwai
AU  - Tsai YH
FAU - Dempsey, Peter J
AU  - Dempsey PJ
FAU - Samuelson, Linda C
AU  - Samuelson LC
LA  - eng
GR  - R01 AI091627/AI/NIAID NIH HHS/United States
GR  - R01 DK065850/DK/NIDDK NIH HHS/United States
GR  - R01 DK056882/DK/NIDDK NIH HHS/United States
GR  - P30 DK34933/DK/NIDDK NIH HHS/United States
GR  - T32 GM007315/GM/NIGMS NIH HHS/United States
GR  - R01-DK56882/DK/NIDDK NIH HHS/United States
GR  - P30 DK034933/DK/NIDDK NIH HHS/United States
GR  - R01 DK078927/DK/NIDDK NIH HHS/United States
GR  - R01-DK78927/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20111221
PL  - England
TA  - Development
JT  - Development (Cambridge, England)
JID - 8701744
RN  - 0 (Atoh1 protein, mouse)
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (Immunoglobulin J Recombination Signal Sequence-Binding Protein)
RN  - 0 (Notch1 protein, mouse)
RN  - 0 (Notch2 protein, mouse)
RN  - 0 (Receptor, Notch1)
RN  - 0 (Receptor, Notch2)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Base Sequence
MH  - Basic Helix-Loop-Helix Transcription Factors/genetics
MH  - *Cell Differentiation
MH  - *Cell Proliferation
MH  - *Gene Expression Regulation
MH  - Goblet Cells/metabolism
MH  - Immunoglobulin J Recombination Signal Sequence-Binding Protein/metabolism
MH  - Intestine, Small/*cytology/drug effects/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Molecular Sequence Data
MH  - Organ Culture Techniques
MH  - Paneth Cells/metabolism
MH  - Promoter Regions, Genetic
MH  - Receptor, Notch1/antagonists & inhibitors/*metabolism
MH  - Receptor, Notch2/antagonists & inhibitors/*metabolism
MH  - Signal Transduction
MH  - Stem Cells/cytology/physiology
PMC - PMC3252352
EDAT- 2011/12/23 06:00
MHDA- 2012/03/07 06:00
PMCR- 2013/02/01
CRDT- 2011/12/23 06:00
PHST- 2011/12/23 06:00 [entrez]
PHST- 2011/12/23 06:00 [pubmed]
PHST- 2012/03/07 06:00 [medline]
PHST- 2013/02/01 00:00 [pmc-release]
AID - dev.070763 [pii]
AID - 10.1242/dev.070763 [doi]
PST - ppublish
SO  - Development. 2012 Feb;139(3):488-97. doi: 10.1242/dev.070763. Epub 2011 Dec 21.