The biophysical property of the limbal niche maintains stemness through YAP

The cell fate decisions of stem cells (SCs) largely depend on signals from their microenvironment (niche). However, very little is known about how biochemical niche cues control cell behavior in vivo. To address this question, we focused on the corneal epithelial SC model in which the SC niche, know...

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Published in:Cell death and differentiation 2023-06, Vol.30 (6), p.1601-1614
Main Authors: Bhattacharya, Swarnabh, Mukherjee, Abhishek, Pisano, Sabrina, Dimri, Shalini, Knaane, Eman, Altshuler, Anna, Nasser, Waseem, Dey, Sunanda, Shi, Lidan, Mizrahi, Ido, Blum, Noam, Jokel, Ophir, Amitai-Lange, Aya, Kaganovsky, Anna, Mimouni, Michael, Socea, Sergiu, Midlij, Mohamad, Tiosano, Beatrice, Hasson, Peleg, Feral, Chloe, Wolfenson, Haguy, Shalom-Feuerstein, Ruby
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Language:English
Subjects:
13/100
13/106
14/19
14/3
38/89
631/208/199
631/208/200
631/67/71
Apoptosis
Biochemistry
Biomechanics
Biomedical and Life Sciences
Cell Biology
Cell Cycle Analysis
Cell Differentiation
Cell fate
Cornea
Epithelium, Corneal - metabolism
Homeostasis
Humans
Life Sciences
Limbus Corneae
Localization
Mechanotransduction
Mechanotransduction, Cellular
Microenvironments
Smad2 protein
Stem Cell Niche
Stem Cells
Stem Cells - metabolism
YAP-Signaling Proteins - metabolism
Yes-associated protein
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cited_by cdi_FETCH-LOGICAL-c475t-e75254a57968c22c885f48e26ce745f16266b25585200c16d774724660ff66273
cites cdi_FETCH-LOGICAL-c475t-e75254a57968c22c885f48e26ce745f16266b25585200c16d774724660ff66273
container_end_page 1614
container_issue 6
container_start_page 1601
container_title Cell death and differentiation
container_volume 30
creator Bhattacharya, Swarnabh
Mukherjee, Abhishek
Pisano, Sabrina
Dimri, Shalini
Knaane, Eman
Altshuler, Anna
Nasser, Waseem
Dey, Sunanda
Shi, Lidan
Mizrahi, Ido
Blum, Noam
Jokel, Ophir
Amitai-Lange, Aya
Kaganovsky, Anna
Mimouni, Michael
Socea, Sergiu
Midlij, Mohamad
Tiosano, Beatrice
Hasson, Peleg
Feral, Chloe
Wolfenson, Haguy
Shalom-Feuerstein, Ruby
description The cell fate decisions of stem cells (SCs) largely depend on signals from their microenvironment (niche). However, very little is known about how biochemical niche cues control cell behavior in vivo. To address this question, we focused on the corneal epithelial SC model in which the SC niche, known as the limbus, is spatially segregated from the differentiation compartment. We report that the unique biomechanical property of the limbus supports the nuclear localization and function of Yes-associated protein (YAP), a putative mediator of the mechanotransduction pathway. Perturbation of tissue stiffness or YAP activity affects SC function as well as tissue integrity under homeostasis and significantly inhibited the regeneration of the SC population following SC depletion. In vitro experiments revealed that substrates with the rigidity of the corneal differentiation compartment inhibit nuclear YAP localization and induce differentiation, a mechanism that is mediated by the TGFβ−SMAD2/3 pathway. Taken together, these results indicate that SC sense biomechanical niche signals and that manipulation of mechano-sensory machinery or its downstream biochemical output may bear fruits in SC expansion for regenerative therapy.
doi_str_mv 10.1038/s41418-023-01156-7
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ispartof Cell death and differentiation, 2023-06, Vol.30 (6), p.1601-1614
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source Springer Nature; PubMed Central
subjects 13/100
13/106
14/19
14/3
38/89
631/208/199
631/208/200
631/67/71
Apoptosis
Biochemistry
Biomechanics
Biomedical and Life Sciences
Cell Biology
Cell Cycle Analysis
Cell Differentiation
Cell fate
Cornea
Epithelium, Corneal - metabolism
Homeostasis
Humans
Life Sciences
Limbus Corneae
Localization
Mechanotransduction
Mechanotransduction, Cellular
Microenvironments
Smad2 protein
Stem Cell Niche
Stem Cells
Stem Cells - metabolism
YAP-Signaling Proteins - metabolism
Yes-associated protein
title The biophysical property of the limbal niche maintains stemness through YAP
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