Sex differences influence intestinal epithelial stem cell proliferation independent of obesity

Zhou, Weinan; Davis, Elizabeth A.; Li, Kailiang; Nowak, Romana A.; Dailey, Murray D.

doi:10.14814/phy2.13746

Cited by 17 publications

(13 citation statements)

References 56 publications

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“…The strong proliferative capacities of ISC and progenitors from female mice allowed the development of a higher number and size of colonoids from bottom crypts, as compared to males. This observation is in accordance with the recent data of Zhou and collaborators [25]. Moreover, this sexual dimorphism in ISC and progenitor proliferation depends on intrinsic mechanisms since the culture of epithelial cells as colonoids was exempt from stroma.…”

Section: Discussionsupporting

confidence: 93%

“…We found that important regulators of the ISC proliferation (β catenin/Wnt pathway, ADAM10/Notch pathway) displayed gene overexpression in female-derived crypts compared to males. However, female- and male-derived crypts did not show significant differences in gene expression of immature markers CD44 and CD24 (our data) and in their size in vivo [25], suggesting sex-specific regulation of proliferative and differentiation pathways at the progenitor level.…”

Section: Discussionmentioning

confidence: 89%

“…Moreover, this sexual dimorphism in ISC and progenitor proliferation depends on intrinsic mechanisms since the culture of epithelial cells as colonoids was exempt from stroma. Zhou and collaborators [25] also found that proliferation of intestinal organoids was not influenced by estrogens. In drosophila, Hudry and collaborators [5] demonstrated that cell-intrinsic mechanisms linked to sex determination genes control cell cycle duration in female ISC.…”

Section: Discussionmentioning

confidence: 99%

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Sexual dimorphism in PAR2-dependent regulation of primitive colonic cells

et al. 2019

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Background Sexual dimorphism in biological responses is a critical knowledge for therapeutic proposals. However, gender differences in intestinal stem cell physiology have been poorly studied. Given the important role of the protease-activated receptor PAR 2 in the control of colon epithelial primitive cells and cell cycle genes, we have performed a sex-based comparison of its expression and of the effects of PAR 2 activation or knockout on cell proliferation and survival functions. Methods Epithelial primitive cells isolated from colons from male and female mice were cultured as colonoids, and their number and size were measured. PAR 2 activation was triggered by the addition of SLIGRL agonist peptide in the culture medium. PAR 2 -deficient mice were used to study the impact of PAR 2 expression on colon epithelial cell culture and gene expression. Results Colonoids from female mice were more abundant and larger compared to males, and these differences were further increased after PAR 2 activation by specific PAR 2 agonist peptide. The proliferation of male epithelial cells was lower compared to females but was specifically increased in PAR 2 knockout male cells. PAR 2 expression was higher in male colon cells compared to females and controlled the gene expression and activation of key negative signals of the primitive cell proliferation. This PAR 2 -dependent brake on the proliferation of male colon primitive cells was correlated with stress resistance. Conclusions Altogether, these data demonstrate that there is a sexual dimorphism in the PAR 2 -dependent regulation of primitive cells of the colon crypt. Electronic supplementary material The online version of this article (10.1186/s13293-019-0262-6) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

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Sexual dimorphism in PAR2-dependent regulation of primitive colonic cells

et al. 2019

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“…Similar results were obtained in the study by Beyaz et al (18), in that an HFd enhanced the stemness and tumorigenicity of intestinal progenitor cells, suggesting that an HFd enhances regeneration. a recent study revealed that iScs in females have greater proliferative ability as compared with those in males (35). The results of the present study indicated that female mice fed an HFd exhibited increased iSc counts, while crypts obtained from mice fed an HFd were more likely to form mini-intestine organoids in a 3d culture, which may partially account for the increase in intestinal tumors in obese individuals.…”

Section: Discussionsupporting

confidence: 56%

Impact of a high‑fat diet on intestinal stem cells and epithelial barrier function in middle‑aged female mice

Xie

Ding

et al. 2020

Mol Med Report

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a high-fat diet (HFd) or obesity-promoting diet is closely associated with metabolic diseases and intestinal tumors, particularly in middle-aged individuals (typically 45-64 years old). The intestinal epithelium constitutes a barrier that separates the host from the food and microbiota in the gut, and thus, a dysfunctional epithelium is associated with a number of diseases. However, the changes caused to the function of intestinal epithelium in response to an HFd have not been well-studied to date. in the present study, middle-aged female mice (12 months old) fed an HFd for a period of 14 weeks were used to determine the effects of HFd on the intestine. characteristics including the body weight, fat deposition, glucose metabolism, inflammatory state and intestinal morphology were assessed, while the intestinal stem cell (iSc) counts and the ability of isolated intestinal crypts to form organoid bodies in 3d culture were examined. intestinal epithelial barrier function, including secretory defense, tight junctions and cell apoptosis, were also studied. Morphologically, the HFd resulted in a mild reduction in the length of villi of the small intestine, the colon length and the depth of colon crypts. in addition, the iSc counts were increased in the small intestine and colon in HFd-fed mice. The ability of crypts to grow into organoids (mini-guts) was also increased in crypts obtained from mice fed an HFd, while HFd compromised the epithelial barrier function of the colon. These results demonstrated how an HFd affects the intestinal epithelium and highlighted the need to carefully consider dietary patterns.

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“…5). По данным W. Zhou et al [38], пролиферация эпителиальных клеток тонкой кишки in vitro у мышей выше в криптах, выделенных от самок, по сравнению с криптами, выделенными от самцов. На пролиферативную активность кишечного эпителия значительное влияние оказывают глюкокортикоиды [39].…”

Section: результаты и обсуждениеunclassified

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2020

Clin. Exp. Morphology

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Sex differences influence intestinal epithelial stem cell proliferation independent of obesity

Cited by 17 publications

References 56 publications

Sexual dimorphism in PAR2-dependent regulation of primitive colonic cells

Sexual dimorphism in PAR2-dependent regulation of primitive colonic cells

Impact of a high‑fat diet on intestinal stem cells and epithelial barrier function in middle‑aged female mice

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