PMID- 25835502
OWN - NLM
STAT- MEDLINE
DCOM- 20150728
LR  - 20220316
IS  - 1095-564X (Electronic)
IS  - 0012-1606 (Print)
IS  - 0012-1606 (Linking)
VI  - 402
IP  - 1
DP  - 2015 Jun 1
TI  - Notch receptor regulation of intestinal stem cell homeostasis and crypt 
      regeneration.
PG  - 98-108
LID - S0012-1606(15)00145-1 [pii]
LID - 10.1016/j.ydbio.2015.03.012 [doi]
AB  - The Notch signaling pathway regulates intestinal epithelial cell homeostasis, 
      including stem cell maintenance, progenitor cell proliferation and 
      differentiation. Notch1 and Notch2 receptors are expressed in the epithelium, but 
      individual contributions to these functions are unclear. We used genetic deletion 
      to define receptor roles on stem cell function, cell 
      proliferation/differentiation, and repair after injury. Loss of Notch1 induced a 
      transient secretory cell hyperplasia that spontaneously resolved over time. In 
      contrast, deletion of Notch2 had no secretory cell effect. Compound deletions of 
      Notch1 and Notch2 resulted in a more severe secretory cell hyperplasia than 
      deletion of Notch1 alone. Furthermore, only double deletion of Notch1 and Notch2 
      decreased cell proliferation, suggesting a low threshold for maintenance of 
      proliferation compared to differentiation. Stem cells were affected by deletion 
      of Notch1, with reduced expression of Olfm4 and fewer LGR5(+) stem cells. 
      Deletion of Notch2 had no apparent affect on stem cell homeostasis. However, we 
      observed impaired crypt regeneration after radiation in both Notch1- and 
      Notch2-deleted intestine, suggesting that higher Notch activity is required 
      post-injury. These findings suggest that Notch1 is the primary receptor 
      regulating intestinal stem cell function and that Notch1 and Notch2 together 
      regulate epithelial cell proliferation, cell fate determination, and post-injury 
      regeneration.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Carulli, Alexis J
AU  - Carulli AJ
AD  - Department of Molecular and Integrative Physiology, University of Michigan, Ann 
      Arbor, MI, USA.
FAU - Keeley, Theresa M
AU  - Keeley TM
AD  - Department of Molecular and Integrative Physiology, University of Michigan, Ann 
      Arbor, MI, USA.
FAU - Demitrack, Elise S
AU  - Demitrack ES
AD  - Department of Molecular and Integrative Physiology, University of Michigan, Ann 
      Arbor, MI, USA.
FAU - Chung, Jooho
AU  - Chung J
AD  - Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA.
FAU - Maillard, Ivan
AU  - Maillard I
AD  - Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA; Department 
      of Internal Medicine, University of Michigan, Ann Arbor, MI, USA; Department of 
      Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, USA.
FAU - Samuelson, Linda C
AU  - Samuelson LC
AD  - Department of Molecular and Integrative Physiology, University of Michigan, Ann 
      Arbor, MI, USA; Department of Internal Medicine, University of Michigan, Ann 
      Arbor, MI, USA. Electronic address: lcsam@umich.edu.
LA  - eng
GR  - P01 DK062041/DK/NIDDK NIH HHS/United States
GR  - R01 AI091627/AI/NIAID NIH HHS/United States
GR  - T32-GM07863/GM/NIGMS NIH HHS/United States
GR  - T32-HD007515/HD/NICHD NIH HHS/United States
GR  - T32 HD007505/HD/NICHD NIH HHS/United States
GR  - T32 GM007863/GM/NIGMS NIH HHS/United States
GR  - R01 DK096972/DK/NIDDK NIH HHS/United States
GR  - P30 DK034933/DK/NIDDK NIH HHS/United States
GR  - F30 DK095517/DK/NIDDK NIH HHS/United States
GR  - R01-DK078927/DK/NIDDK NIH HHS/United States
GR  - P30-DK34933/DK/NIDDK NIH HHS/United States
GR  - F30-DK095517/DK/NIDDK NIH HHS/United States
GR  - R01-AI091627/AI/NIAID NIH HHS/United States
GR  - P01-DK062041/DK/NIDDK NIH HHS/United States
GR  - R01 DK078927/DK/NIDDK NIH HHS/United States
GR  - T32 GM007315/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150330
PL  - United States
TA  - Dev Biol
JT  - Developmental biology
JID - 0372762
RN  - 0 (Notch1 protein, mouse)
RN  - 0 (Receptor, Notch1)
RN  - 0 (Receptor, Notch2)
SB  - IM
MH  - Animals
MH  - Cell Differentiation
MH  - Cell Lineage
MH  - Cell Proliferation
MH  - Crosses, Genetic
MH  - *Gene Deletion
MH  - Gene Expression Profiling
MH  - *Gene Expression Regulation
MH  - Gene Expression Regulation, Developmental
MH  - Homeostasis
MH  - Hyperplasia/metabolism
MH  - Intestinal Mucosa/*metabolism
MH  - Intestines/cytology/embryology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Receptor, Notch1/*metabolism
MH  - Receptor, Notch2/*metabolism
MH  - Stem Cells/*cytology
PMC - PMC4433599
MID - NIHMS676666
OTO - NOTNLM
OT  - Cell fate determination
OT  - Irradiation injury
OT  - Notch signaling
OT  - Notch1, Notch2, crypt base columnar stem cell
OT  - Olfm4, Lgr5, goblet cell hyperplasia
EDAT- 2015/04/04 06:00
MHDA- 2015/07/29 06:00
PMCR- 2016/06/01
CRDT- 2015/04/04 06:00
PHST- 2014/07/02 00:00 [received]
PHST- 2015/03/07 00:00 [revised]
PHST- 2015/03/20 00:00 [accepted]
PHST- 2015/04/04 06:00 [entrez]
PHST- 2015/04/04 06:00 [pubmed]
PHST- 2015/07/29 06:00 [medline]
PHST- 2016/06/01 00:00 [pmc-release]
AID - S0012-1606(15)00145-1 [pii]
AID - 10.1016/j.ydbio.2015.03.012 [doi]
PST - ppublish
SO  - Dev Biol. 2015 Jun 1;402(1):98-108. doi: 10.1016/j.ydbio.2015.03.012. Epub 2015 
      Mar 30.