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Pigs, unlike mice, have two distinct colonic stem cell populations similar to humans that respond to high-calorie diet prior to insulin resistance

Charepalli, Venkata; Reddivari, Lavanya; Radhakrishnan, Sridhar; Eriksson, Elisabeth LU ; Xiao, Xia; Kim, Sung Woo; Shen, Frank; Vijay-Kumar, Matam; Li, Qunhua and Bhat, Vadiraja B., et al. (2017) In Cancer Prevention Research 10(8). p.442-450
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... (More)

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.

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Cancer Prevention Research
volume
10
issue
8
pages
9 pages
publisher
American Association for Cancer Research
external identifiers
  • scopus:85027051502
  • wos:000406776300003
ISSN
1940-6207
DOI
10.1158/1940-6207.CAPR-17-0010
language
English
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yes
id
61e17856-a3cc-470e-9ebe-20383b911baa
date added to LUP
2017-09-07 08:42:39
date last changed
2018-01-07 12:18:13
@article{61e17856-a3cc-470e-9ebe-20383b911baa,
  abstract     = {<p>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.</p>},
  author       = {Charepalli, Venkata and Reddivari, Lavanya and Radhakrishnan, Sridhar and Eriksson, Elisabeth and Xiao, Xia and Kim, Sung Woo and Shen, Frank and Vijay-Kumar, Matam and Li, Qunhua and Bhat, Vadiraja B. and Knight, Rob and Vanamala, Jairam K P},
  issn         = {1940-6207},
  language     = {eng},
  month        = {08},
  number       = {8},
  pages        = {442--450},
  publisher    = {American Association for Cancer Research},
  series       = {Cancer Prevention Research},
  title        = {Pigs, unlike mice, have two distinct colonic stem cell populations similar to humans that respond to high-calorie diet prior to insulin resistance},
  url          = {http://dx.doi.org/10.1158/1940-6207.CAPR-17-0010},
  volume       = {10},
  year         = {2017},
}