PMID- 17881565
OWN - NLM
STAT- MEDLINE
DCOM- 20071026
LR  - 20220317
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 104
IP  - 39
DP  - 2007 Sep 25
TI  - Gene expression patterns of human colon tops and basal crypts and BMP antagonists 
      as intestinal stem cell niche factors.
PG  - 15418-23
AB  - Human colonic epithelial cell renewal, proliferation, and differentiation are 
      stringently controlled by numerous regulatory pathways. To identify genetic 
      programs of human colonic epithelial cell differentiation in vivo as well as 
      candidate marker genes that define colonic epithelial stem/progenitor cells and 
      the stem cell niche, we applied gene expression analysis of normal human colon 
      tops and basal crypts by using expression microarrays with 30,000 genes. Nine 
      hundred and sixty-nine cDNA clones were found to be differentially expressed 
      between human colon crypts and tops. Pathway analysis revealed the differential 
      expression of genes involved in cell cycle maintenance and apoptosis, as well as 
      genes in bone morphogenetic protein (BMP), Notch, Wnt, EPH, and MYC signaling 
      pathways. BMP antagonists gremlin 1, gremlin 2, and chordin-like 1 were found to 
      be expressed by colon crypts. In situ hybridization and RT-PCR confirmed that 
      these BMP antagonists are expressed by intestinal cryptal myofibroblasts and 
      smooth muscle cells at the colon crypt. In vitro analysis demonstrated that 
      gremlin 1 partially inhibits Caco-2 cell differentiation upon confluence and 
      activates Wnt signaling in normal rat intestinal epithelial cells. Collectively, 
      the expression data set provides a comprehensive picture of human colonic 
      epithelial cell differentiation. Our study also suggests that BMP antagonists are 
      candidate signaling components that make up the intestinal epithelial stem cell 
      niche.
FAU - Kosinski, Cynthia
AU  - Kosinski C
AD  - Department of Biopharmaceutical Sciences, University of California, San 
      Francisco, CA 94143, USA.
FAU - Li, Vivian S W
AU  - Li VS
FAU - Chan, Annie S Y
AU  - Chan AS
FAU - Zhang, Ji
AU  - Zhang J
FAU - Ho, Coral
AU  - Ho C
FAU - Tsui, Wai Yin
AU  - Tsui WY
FAU - Chan, Tsun Leung
AU  - Chan TL
FAU - Mifflin, Randy C
AU  - Mifflin RC
FAU - Powell, Don W
AU  - Powell DW
FAU - Yuen, Siu Tsan
AU  - Yuen ST
FAU - Leung, Suet Yi
AU  - Leung SY
FAU - Chen, Xin
AU  - Chen X
LA  - eng
SI  - GEO/GSE6894
GR  - R01 DK055783/DK/NIDDK NIH HHS/United States
GR  - R21DK-069309/DK/NIDDK NIH HHS/United States
GR  - R21 DK069309/DK/NIDDK NIH HHS/United States
GR  - R01DK-055783/DK/NIDDK NIH HHS/United States
GR  - K01 CA096774/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070919
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Bone Morphogenetic Proteins)
RN  - 0 (CHRDL1 protein, human)
RN  - 0 (Cytokines)
RN  - 0 (Eye Proteins)
RN  - 0 (GREM1 protein, human)
RN  - 0 (GREM2 protein, human)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Receptors, Notch)
SB  - IM
MH  - Apoptosis
MH  - Bone Morphogenetic Proteins/*metabolism
MH  - Caco-2 Cells
MH  - Colon/*metabolism
MH  - Cytokines
MH  - Epithelial Cells/metabolism
MH  - Eye Proteins/biosynthesis
MH  - *Gene Expression Profiling
MH  - *Gene Expression Regulation
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/biosynthesis
MH  - Intestinal Mucosa/*metabolism
MH  - Nerve Tissue Proteins/biosynthesis
MH  - Receptors, Notch/metabolism
MH  - Signal Transduction
MH  - Stem Cells/*metabolism
PMC - PMC2000506
COIS- The authors declare no conflict of interest.
EDAT- 2007/09/21 09:00
MHDA- 2007/10/30 09:00
PMCR- 2008/03/25
CRDT- 2007/09/21 09:00
PHST- 2007/09/21 09:00 [pubmed]
PHST- 2007/10/30 09:00 [medline]
PHST- 2007/09/21 09:00 [entrez]
PHST- 2008/03/25 00:00 [pmc-release]
AID - 0707210104 [pii]
AID - 7675 [pii]
AID - 10.1073/pnas.0707210104 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2007 Sep 25;104(39):15418-23. doi: 
      10.1073/pnas.0707210104. Epub 2007 Sep 19.