PMID- 21995959
OWN - NLM
STAT- MEDLINE
DCOM- 20120216
LR  - 20240629
IS  - 1522-1547 (Electronic)
IS  - 0193-1857 (Print)
IS  - 0193-1857 (Linking)
VI  - 302
IP  - 1
DP  - 2012 Jan 1
TI  - Distinct levels of Sox9 expression mark colon epithelial stem cells that form 
      colonoids in culture.
PG  - G10-20
LID - 10.1152/ajpgi.00277.2011 [doi]
AB  - Sox9 is an high-mobility group box transcription factor that is expressed in the 
      stem cell zone of the small intestine and colon. We have previously used a 
      Sox9EGFP mouse model to demonstrate that discrete levels of Sox9 expression mark 
      small intestine epithelial stem cells that form crypt/villus-like structures in a 
      three-dimensional culture system (Formeister EJ, Sionas AL, Lorance DK, Barkley 
      CL, Lee GH, Magness ST. Am J Physiol Gastrointest Liver Physiol 296: G1108-G1118, 
      2009; Gracz AD, Ramalingam S, Magness ST. Am J Physiol Gastrointest Liver Physiol 
      298: G590-G600, 2010). In the present study, we hypothesized that discrete levels 
      of Sox9 expression would also mark colonic epithelial stem cells (CESCs). Using 
      the Sox9EGFP mouse model, we show that lower levels of Sox9 mark cells in the 
      transit-amplifying progenitor cell zone, while higher levels of Sox9 mark cells 
      in the colonic crypt base. Furthermore, we demonstrate that variable SOX9 levels 
      persist in cells of colonic adenomas from mice and humans. Cells expressing lower 
      Sox9 levels demonstrate gene expression profiles consistent with more 
      differentiated populations, and cells expressing higher Sox9 levels are 
      consistent with less differentiated populations. When placed in culture, cells 
      expressing the highest levels of Sox9 formed "colonoids," which are defined as 
      bodies of cultured colonic epithelial cells that possess multiple cryptlike 
      structures and a pseudolumen. Cells expressing the highest levels of Sox9 also 
      demonstrate multipotency and self-renewal in vitro, indicating functional 
      stemness. These data suggest a dose-dependent role for Sox9 in normal CESCs and 
      cells comprising colon tumors. Furthermore, distinct Sox9 levels represent a new 
      biomarker to study CESC and progenitor biology in physiological and disease 
      states.
FAU - Ramalingam, S
AU  - Ramalingam S
AD  - Department of Medicine, Division of Gastroenterology and Hepatology, University 
      of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
FAU - Daughtridge, G W
AU  - Daughtridge GW
FAU - Johnston, M J
AU  - Johnston MJ
FAU - Gracz, A D
AU  - Gracz AD
FAU - Magness, S T
AU  - Magness ST
LA  - eng
GR  - K01 DK080181/DK/NIDDK NIH HHS/United States
GR  - P30-DK034987/DK/NIDDK NIH HHS/United States
GR  - 5-P50-CA 106991/CA/NCI NIH HHS/United States
GR  - K01-DK080181/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 - 20111013
PL  - United States
TA  - Am J Physiol Gastrointest Liver Physiol
JT  - American journal of physiology. Gastrointestinal and liver physiology
JID - 100901227
RN  - 0 (SOX9 Transcription Factor)
RN  - 0 (Sox9 protein, mouse)
SB  - IM
MH  - Adenoma/genetics/*metabolism
MH  - Animals
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - Colon/*metabolism
MH  - Colonic Neoplasms/genetics/*metabolism
MH  - Female
MH  - Gene Expression Profiling
MH  - Humans
MH  - Intestinal Mucosa/metabolism
MH  - Male
MH  - Mice
MH  - SOX9 Transcription Factor/*biosynthesis
MH  - Stem Cells/metabolism
PMC - PMC3345960
EDAT- 2011/10/15 06:00
MHDA- 2012/02/18 06:00
PMCR- 2013/01/01
CRDT- 2011/10/15 06:00
PHST- 2011/10/15 06:00 [entrez]
PHST- 2011/10/15 06:00 [pubmed]
PHST- 2012/02/18 06:00 [medline]
PHST- 2013/01/01 00:00 [pmc-release]
AID - ajpgi.00277.2011 [pii]
AID - GI-00277-2011 [pii]
AID - 10.1152/ajpgi.00277.2011 [doi]
PST - ppublish
SO  - Am J Physiol Gastrointest Liver Physiol. 2012 Jan 1;302(1):G10-20. doi: 
      10.1152/ajpgi.00277.2011. Epub 2011 Oct 13.