Cellular shape reinforces niche to stem cell signaling in the small intestine

Nalle Pentinmikko; Rodrigo Lozano; Sandra Scharaw; Simon Andersson; Johanna I. Englund; David Castillo-Azofeifa; Aaron Gallagher; Martin Broberg; Ki Young Song; Agustín Sola Carvajal; Alessondra T. Speidel; Michael Sundstrom; Nancy Allbritton; Molly M. Stevens; Ophir D. Klein; Ana Teixeira; Pekka Katajisto

doi:10.1126/sciadv.abm1847

Cellular shape reinforces niche to stem cell signaling in the small intestine

Nalle Pentinmikko, Rodrigo Lozano, Sandra Scharaw, Simon Andersson, Johanna I. Englund, David Castillo-Azofeifa, Aaron Gallagher, Martin Broberg, Ki Young Song, Agustín Sola Carvajal, Alessondra T. Speidel, Michael Sundstrom, Nancy Allbritton, Molly M. Stevens, Ophir D. Klein, Ana Teixeira, Pekka Katajisto^*

^*Corresponding author for this work

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

14 Citations (Scopus)

Abstract

Niche-derived factors regulate tissue stem cells, but apart from the mechanosensory pathways, the effect of niche geometry is not well understood. We used organoids and bioengineered tissue culture platforms to demonstrate that the conical shape of Lgr5⁺ small intestinal stem cells (ISCs) facilitate their self-renewal and function. Inhibition of non-muscle myosin II (NM II)-driven apical constriction altered ISC shape and reduced niche curvature and stem cell capacity. Niche curvature is decreased in aged mice, suggesting that suboptimal interactions between old ISCs and their niche develop with age. We show that activation of NM IIC or physical restriction to young topology improves in vitro regeneration by old epithelium. We propose that the increase in lateral surface area of ISCs induced by apical constriction promotes interactions between neighboring cells, and the curved topology of the intestinal niche has evolved to maximize signaling between ISCs and neighboring cells.

Original language	English
Article number	eabm1847
Journal	Science advances
Volume	8
Issue number	41
DOIs	https://doi.org/10.1126/sciadv.abm1847
Publication status	Published - Oct 2022
Externally published	Yes

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Pentinmikko, N., Lozano, R., Scharaw, S., Andersson, S., Englund, J. I., Castillo-Azofeifa, D., Gallagher, A., Broberg, M., Song, K. Y., Carvajal, A. S., Speidel, A. T., Sundstrom, M., Allbritton, N., Stevens, M. M., Klein, O. D., Teixeira, A., & Katajisto, P. (2022). Cellular shape reinforces niche to stem cell signaling in the small intestine. Science advances, 8(41), Article eabm1847. https://doi.org/10.1126/sciadv.abm1847

@article{0ece7233971a4553a029beae35ae91fc,

title = "Cellular shape reinforces niche to stem cell signaling in the small intestine",

abstract = "Niche-derived factors regulate tissue stem cells, but apart from the mechanosensory pathways, the effect of niche geometry is not well understood. We used organoids and bioengineered tissue culture platforms to demonstrate that the conical shape of Lgr5+ small intestinal stem cells (ISCs) facilitate their self-renewal and function. Inhibition of non-muscle myosin II (NM II)-driven apical constriction altered ISC shape and reduced niche curvature and stem cell capacity. Niche curvature is decreased in aged mice, suggesting that suboptimal interactions between old ISCs and their niche develop with age. We show that activation of NM IIC or physical restriction to young topology improves in vitro regeneration by old epithelium. We propose that the increase in lateral surface area of ISCs induced by apical constriction promotes interactions between neighboring cells, and the curved topology of the intestinal niche has evolved to maximize signaling between ISCs and neighboring cells.",

author = "Nalle Pentinmikko and Rodrigo Lozano and Sandra Scharaw and Simon Andersson and Englund, {Johanna I.} and David Castillo-Azofeifa and Aaron Gallagher and Martin Broberg and Song, {Ki Young} and Carvajal, {Agust{\'i}n Sola} and Speidel, {Alessondra T.} and Michael Sundstrom and Nancy Allbritton and Stevens, {Molly M.} and Klein, {Ophir D.} and Ana Teixeira and Pekka Katajisto",

note = "Publisher Copyright: Copyright {\textcopyright} 2022 The Authors, some rights reserved.",

year = "2022",

month = oct,

doi = "10.1126/sciadv.abm1847",

language = "English",

volume = "8",

journal = "Science advances",

issn = "2375-2548",

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Pentinmikko, N, Lozano, R, Scharaw, S, Andersson, S, Englund, JI, Castillo-Azofeifa, D, Gallagher, A, Broberg, M, Song, KY, Carvajal, AS, Speidel, AT, Sundstrom, M, Allbritton, N, Stevens, MM, Klein, OD, Teixeira, A & Katajisto, P 2022, 'Cellular shape reinforces niche to stem cell signaling in the small intestine', Science advances, vol. 8, no. 41, eabm1847. https://doi.org/10.1126/sciadv.abm1847

TY - JOUR

T1 - Cellular shape reinforces niche to stem cell signaling in the small intestine

AU - Pentinmikko, Nalle

AU - Lozano, Rodrigo

AU - Scharaw, Sandra

AU - Andersson, Simon

AU - Englund, Johanna I.

AU - Castillo-Azofeifa, David

AU - Gallagher, Aaron

AU - Broberg, Martin

AU - Song, Ki Young

AU - Carvajal, Agustín Sola

AU - Speidel, Alessondra T.

AU - Sundstrom, Michael

AU - Allbritton, Nancy

AU - Stevens, Molly M.

AU - Klein, Ophir D.

AU - Teixeira, Ana

AU - Katajisto, Pekka

PY - 2022/10

Y1 - 2022/10

N2 - Niche-derived factors regulate tissue stem cells, but apart from the mechanosensory pathways, the effect of niche geometry is not well understood. We used organoids and bioengineered tissue culture platforms to demonstrate that the conical shape of Lgr5+ small intestinal stem cells (ISCs) facilitate their self-renewal and function. Inhibition of non-muscle myosin II (NM II)-driven apical constriction altered ISC shape and reduced niche curvature and stem cell capacity. Niche curvature is decreased in aged mice, suggesting that suboptimal interactions between old ISCs and their niche develop with age. We show that activation of NM IIC or physical restriction to young topology improves in vitro regeneration by old epithelium. We propose that the increase in lateral surface area of ISCs induced by apical constriction promotes interactions between neighboring cells, and the curved topology of the intestinal niche has evolved to maximize signaling between ISCs and neighboring cells.

AB - Niche-derived factors regulate tissue stem cells, but apart from the mechanosensory pathways, the effect of niche geometry is not well understood. We used organoids and bioengineered tissue culture platforms to demonstrate that the conical shape of Lgr5+ small intestinal stem cells (ISCs) facilitate their self-renewal and function. Inhibition of non-muscle myosin II (NM II)-driven apical constriction altered ISC shape and reduced niche curvature and stem cell capacity. Niche curvature is decreased in aged mice, suggesting that suboptimal interactions between old ISCs and their niche develop with age. We show that activation of NM IIC or physical restriction to young topology improves in vitro regeneration by old epithelium. We propose that the increase in lateral surface area of ISCs induced by apical constriction promotes interactions between neighboring cells, and the curved topology of the intestinal niche has evolved to maximize signaling between ISCs and neighboring cells.

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DO - 10.1126/sciadv.abm1847

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SN - 2375-2548

VL - 8

JO - Science advances

JF - Science advances

IS - 41

M1 - eabm1847

ER -

Cellular shape reinforces niche to stem cell signaling in the small intestine

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