YAP and ECM Stiffness: Key Drivers of Adipocyte Differentiation and Lipid Accumulation

ECM stiffness significantly influences the differentiation of adipose-derived stem cells (ADSCs), with YAP—a key transcription factor in the Hippo signaling pathway—playing a pivotal role. This study investigates the effects of ECM stiffness on ADSC differentiation and its relationship with YAP sign...

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Main Authors: Da-Long Dong, Guang-Zhen Jin
Format: Article
Language:English
Published: MDPI AG 2024-11-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/13/22/1905
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author Da-Long Dong
Guang-Zhen Jin
author_facet Da-Long Dong
Guang-Zhen Jin
author_sort Da-Long Dong
collection DOAJ
description ECM stiffness significantly influences the differentiation of adipose-derived stem cells (ADSCs), with YAP—a key transcription factor in the Hippo signaling pathway—playing a pivotal role. This study investigates the effects of ECM stiffness on ADSC differentiation and its relationship with YAP signaling. Various hydrogel concentrations were employed to simulate different levels of ECM stiffness, and their impact on ADSC differentiation was assessed through material properties, adipocyte-specific gene expression, lipid droplet staining, YAP localization, and protein levels. Our results demonstrated that increasing hydrogel stiffness enhanced adipocyte differentiation in a gradient manner. Notably, inhibiting YAP signaling further increased lipid droplet accumulation, suggesting that ECM stiffness influences adipogenesis by modulating YAP signaling and its cytoplasmic phosphorylation. This study elucidates the molecular mechanisms underlying ECM stiffness-dependent lipid deposition, highlighting YAP’s regulatory role in adipogenesis. These findings provide valuable insights into the regulation of cell differentiation and have important implications for tissue engineering and obesity treatment strategies.
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spelling doaj-art-9840ab8a22ae40e2b3e98ff1e78977432025-08-20T02:28:08ZengMDPI AGCells2073-44092024-11-011322190510.3390/cells13221905YAP and ECM Stiffness: Key Drivers of Adipocyte Differentiation and Lipid AccumulationDa-Long Dong0Guang-Zhen Jin1Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 31116, Republic of KoreaInstitute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 31116, Republic of KoreaECM stiffness significantly influences the differentiation of adipose-derived stem cells (ADSCs), with YAP—a key transcription factor in the Hippo signaling pathway—playing a pivotal role. This study investigates the effects of ECM stiffness on ADSC differentiation and its relationship with YAP signaling. Various hydrogel concentrations were employed to simulate different levels of ECM stiffness, and their impact on ADSC differentiation was assessed through material properties, adipocyte-specific gene expression, lipid droplet staining, YAP localization, and protein levels. Our results demonstrated that increasing hydrogel stiffness enhanced adipocyte differentiation in a gradient manner. Notably, inhibiting YAP signaling further increased lipid droplet accumulation, suggesting that ECM stiffness influences adipogenesis by modulating YAP signaling and its cytoplasmic phosphorylation. This study elucidates the molecular mechanisms underlying ECM stiffness-dependent lipid deposition, highlighting YAP’s regulatory role in adipogenesis. These findings provide valuable insights into the regulation of cell differentiation and have important implications for tissue engineering and obesity treatment strategies.https://www.mdpi.com/2073-4409/13/22/1905YAP signalingECM stiffnessadipocyte differentiationhydrogelsmechanotransductionlipid accumulation
spellingShingle Da-Long Dong
Guang-Zhen Jin
YAP and ECM Stiffness: Key Drivers of Adipocyte Differentiation and Lipid Accumulation
Cells
YAP signaling
ECM stiffness
adipocyte differentiation
hydrogels
mechanotransduction
lipid accumulation
title YAP and ECM Stiffness: Key Drivers of Adipocyte Differentiation and Lipid Accumulation
title_full YAP and ECM Stiffness: Key Drivers of Adipocyte Differentiation and Lipid Accumulation
title_fullStr YAP and ECM Stiffness: Key Drivers of Adipocyte Differentiation and Lipid Accumulation
title_full_unstemmed YAP and ECM Stiffness: Key Drivers of Adipocyte Differentiation and Lipid Accumulation
title_short YAP and ECM Stiffness: Key Drivers of Adipocyte Differentiation and Lipid Accumulation
title_sort yap and ecm stiffness key drivers of adipocyte differentiation and lipid accumulation
topic YAP signaling
ECM stiffness
adipocyte differentiation
hydrogels
mechanotransduction
lipid accumulation
url https://www.mdpi.com/2073-4409/13/22/1905
work_keys_str_mv AT dalongdong yapandecmstiffnesskeydriversofadipocytedifferentiationandlipidaccumulation
AT guangzhenjin yapandecmstiffnesskeydriversofadipocytedifferentiationandlipidaccumulation