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Cancer Prev Res (Phila). 2017 Aug;10(8):442-450. doi: 10.1158/1940-6207.CAPR-17-0010. Epub 2017 Jun 2.

Pigs, Unlike Mice, Have Two Distinct Colonic Stem Cell Populations Similar to Humans That Respond to High-Calorie Diet prior to Insulin Resistance.

Author information

1
Department of Food Science, The Pennsylvania State University, University Park, Pennsylvania.
2
Department of Plant Science, The Pennsylvania State University, University Park, Pennsylvania.
3
Biotechnology, Applied Nutrition and Food Chemistry, Lund University, Lund, Sweden.
4
Department of Nutritional Sciences, The Pennsylvania State University, University Park, Pennsylvania.
5
Department of Animal Science, North Carolina State University, Raleigh, North Carolina.
6
Department of Statistics, The Pennsylvania State University, University Park, Pennsylvania.
7
Department of Medicine, The Pennsylvania State University Medical Center, Hershey, Pennsylvania.
8
Agilent Technologies, Wilmington, Delaware.
9
Department of Pediatrics, University of California, San Diego, California.
10
Department of Computer Science and Engineering, University of California, La Jolla, California.
11
Department of Food Science, The Pennsylvania State University, University Park, Pennsylvania. juv4@psu.edu.
12
The Penn State Hershey Cancer Institute, Hershey, Pennsylvania.
13
Center for Molecular Immunology and Infectious Diseases, The Pennsylvania State University, University Park, Pennsylvania.

Abstract

Basal colonic crypt stem cells are long lived and play a role in colon homeostasis. Previous evidence has shown that high-calorie diet (HCD) enhances colonic stem cell numbers and expansion of the proliferative zone, an important biomarker for colon cancer. However, it is not clear how HCD drives dysregulation of colon stem cell/colonocyte proliferative kinetics. We used a human-relevant pig model and developed an immunofluorescence technique to detect and quantify colonic stem cells. Pigs (n = 8/group) were provided either standard diet (SD; 5% fat) or HCD (23% fat) for 13 weeks. HCD- and SD-consuming pigs had similar total calorie intake, serum iron, insulin, and glucose levels. However, HCD elevated both colonic proliferative zone (KI-67) and stem cell zone (ASCL-2 and BMI-1). Proliferative zone correlated with elevated innate colonic inflammatory markers TLR-4, NF-κB, IL6, and lipocalin-2 (r ≥ 0.62, P = 0.02). Elevated gut bacterial phyla proteobacteria and firmicutes in HCD-consuming pigs correlated with proliferative and stem cell zone. Colonic proteome data revealed the upregulation of proteins involved in cell migration and proliferation and correlated with proliferative and stem cell zone expansion. Our study suggests that pig colon, unlike mice, has two distinct stem cells (ASCL-2 and BMI-1) similar to humans, and HCD increases expansion of colonic proliferative and stem cell zone. Thus, pig model can aid in the development of preventive strategies against gut bacterial dysbiosis and inflammation-promoted diseases, such as colon cancer. Cancer Prev Res; 10(8); 442-50. ©2017 AACR.

PMID:
28576788
PMCID:
PMC6188705
DOI:
10.1158/1940-6207.CAPR-17-0010
[Indexed for MEDLINE]
Free PMC Article

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