Colonic CD90+ Crypt Fibroblasts Secrete Semaphorins to Support Epithelial Growth

Olga N Karpus; B Florien Westendorp; Jacqueline L M Vermeulen; Sander Meisner; Jan Koster; Vanesa Muncan; Manon E Wildenberg; Gijs R van den Brink

doi:https://doi.org/10.1016/j.celrep.2019.02.101

Colonic CD90+ Crypt Fibroblasts Secrete Semaphorins to Support Epithelial Growth

Olga N Karpus, B Florien Westendorp, Jacqueline L M Vermeulen, Sander Meisner, Jan Koster, Vanesa Muncan, Manon E Wildenberg, Gijs R van den Brink

Research output: Contribution to journal › Article › Academic › peer-review

61 Citations (Scopus)

Abstract

Intestinal epithelial cells have a defined hierarchy with stem cells located at the bottom of the crypt and differentiated cells more at the top. Epithelial cell renewal and differentiation are strictly controlled by various regulatory signals provided by epithelial as well as surrounding cells. Although there is evidence that stromal cells contribute to the intestinal stem cell niche, their markers and the soluble signals they produce have been incompletely defined. Using a number of established stromal cell markers, we phenotypically and functionally examined fibroblast populations in the colon. CD90+ fibroblasts located in close proximity to stem cells in vivo support organoid growth in vitro and express crucial stem cell growth factors, such as Grem1, Wnt2b, and R-spondin3. Moreover, we found that CD90+ fibroblasts express a family of proteins-class 3 semaphorins (Sema3)-that are required for the supportive effect of CD90+ fibroblasts on organoid growth.

Original language	English
Pages (from-to)	3698-3708.e5
Journal	Cell reports
Volume	26
Issue number	13
DOIs	https://doi.org/10.1016/j.celrep.2019.02.101
Publication status	Published - 26 Mar 2019

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https://doi.org/10.1016/j.celrep.2019.02.101

http://www.cell.com/article/S2211124719302876/pdf

Cite this

@article{203166bfc1cb42b8b6fd85ca7eb4f0b0,

title = "Colonic CD90+ Crypt Fibroblasts Secrete Semaphorins to Support Epithelial Growth",

abstract = "Intestinal epithelial cells have a defined hierarchy with stem cells located at the bottom of the crypt and differentiated cells more at the top. Epithelial cell renewal and differentiation are strictly controlled by various regulatory signals provided by epithelial as well as surrounding cells. Although there is evidence that stromal cells contribute to the intestinal stem cell niche, their markers and the soluble signals they produce have been incompletely defined. Using a number of established stromal cell markers, we phenotypically and functionally examined fibroblast populations in the colon. CD90+ fibroblasts located in close proximity to stem cells in vivo support organoid growth in vitro and express crucial stem cell growth factors, such as Grem1, Wnt2b, and R-spondin3. Moreover, we found that CD90+ fibroblasts express a family of proteins-class 3 semaphorins (Sema3)-that are required for the supportive effect of CD90+ fibroblasts on organoid growth.",

author = "Karpus, {Olga N} and Westendorp, {B Florien} and Vermeulen, {Jacqueline L M} and Sander Meisner and Jan Koster and Vanesa Muncan and Wildenberg, {Manon E} and {van den Brink}, {Gijs R}",

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T1 - Colonic CD90+ Crypt Fibroblasts Secrete Semaphorins to Support Epithelial Growth

AU - Karpus, Olga N

AU - Westendorp, B Florien

AU - Vermeulen, Jacqueline L M

AU - Meisner, Sander

AU - Koster, Jan

AU - Muncan, Vanesa

AU - Wildenberg, Manon E

AU - van den Brink, Gijs R

PY - 2019/3/26

Y1 - 2019/3/26

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AB - Intestinal epithelial cells have a defined hierarchy with stem cells located at the bottom of the crypt and differentiated cells more at the top. Epithelial cell renewal and differentiation are strictly controlled by various regulatory signals provided by epithelial as well as surrounding cells. Although there is evidence that stromal cells contribute to the intestinal stem cell niche, their markers and the soluble signals they produce have been incompletely defined. Using a number of established stromal cell markers, we phenotypically and functionally examined fibroblast populations in the colon. CD90+ fibroblasts located in close proximity to stem cells in vivo support organoid growth in vitro and express crucial stem cell growth factors, such as Grem1, Wnt2b, and R-spondin3. Moreover, we found that CD90+ fibroblasts express a family of proteins-class 3 semaphorins (Sema3)-that are required for the supportive effect of CD90+ fibroblasts on organoid growth.

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DO - https://doi.org/10.1016/j.celrep.2019.02.101

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