@article{aadc37f962ce47f1a49527b5d69eb3d9,
title = "Cofilin-1 Is a mechanosensitive regulator of transcription",
abstract = "The mechanical properties of the extracellular environment are interrogated by cells and integrated through mechanotransduction. Many cellular processes depend on actomyosin-dependent contractility, which is influenced by the microenvironment{\textquoteright}s stiffness. Here, we explored the influence of substrate stiffness on the proteome of proliferating undifferentiated human umbilical cord-matrix mesenchymal stem/stromal cells. The relative abundance of several proteins changed significantly by expanding cells on soft (∼3 kPa) or stiff substrates (GPa). Many such proteins are associated with the regulation of the actin cytoskeleton, a major player of mechanotransduction and cell physiology in response to mechanical cues. Specifically, Cofilin-1 levels were elevated in cells cultured on soft comparing with stiff substrates. Furthermore, Cofilin-1 was de-phosphorylated (active) and present in the nuclei of cells kept on soft substrates, in contrast with phosphorylated (inactive) and widespread distribution in cells on stiff. Soft substrates promoted Cofilin-1-dependent increased RNA transcription and faster RNA polymerase II-mediated transcription elongation. Cofilin-1 is part of a novel mechanism linking mechanotransduction and transcription.",
keywords = "Cofilin-1, Cytoskeleton, hUCM-MSCs, Mechanotransduction, Proteomics, Transcription",
author = "Catarina Domingues and Geraldo, {A. Margarida} and Anjo, {Sandra Isabel} and Andr{\'e} Matos and Cl{\'a}udio Almeida and In{\^e}s Caramelo and Lopes-da-Silva, {Jos{\'e} A.} and Artur Paiva and Jo{\~a}o Carvalho and {Pires das Neves}, Ricardo and Bruno Manadas and M{\'a}rio Gr{\~a}os",
note = "Funding Information: Carla Cardoso, Sofia Couceiro, and Ana Cabeleira from Stemlab S.A. (Crioestaminal) are acknowledged for providing umbilical cord samples. Paula Laranjeira is acknowledged for assistance in flow cytometry. We are thankful to Jurgen A. Marteijn, who provided MRC-5 cells. Funding. This work was supported by the European Regional Development Fund (ERDF), through the COMPETE 2020 – Operational Programme for Competitiveness and Internationalisation and Portuguese national funds via FCT – Funda{\c c}{\~a}o para a Ci{\^e}ncia e a Tecnologia, I.P., under projects: POCI-01-0145-FEDER-029516 (ref.: PTDC/MED-NEU/29516/2017) to MG; POCI-01-0145-FEDER-029311 (ref.: PTDC/BTM-TEC/29311/2017) and POCI-01-0145-FEDER-016428 (ref.: SAICTPAC/0010/2015) to BM; UID/NEU/04539/2019 (CNC.IBILI strategic plan) and UIDB/04539/2020 (CIBB strategic plan). FCT is acknowledged for the Ph.D. fellowships attributed to Catarina Domingues (SFRH/BD/115527/2016) and In{\^e}s Caramelo (SFRH/BD/143442/2019). Funding Information: This work was supported by the European Regional Development Fund (ERDF), through the COMPETE 2020 – Operational Programme for Competitiveness and Internationalisation and Portuguese national funds via FCT – Funda{\c c}{\~a}o para a Ci{\^e}ncia e a Tecnologia, I.P., under projects: POCI-01-0145-FEDER-029516 (ref.: PTDC/MED-NEU/29516/2017) to MG; POCI-01-0145-FEDER-029311 (ref.: PTDC/BTM-TEC/29311/2017) and POCI-01-0145-FEDER-016428 (ref.: SAICTPAC/0010/2015) to BM; UID/NEU/04539/2019 (CNC.IBILI strategic plan) and UIDB/04539/2020 (CIBB strategic plan). FCT is acknowledged for the Ph.D. fellowships attributed to Catarina Domingues (SFRH/BD/115527/2016) and In{\^e}s Caramelo (SFRH/BD/143442/2019). Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 2020 Domingues, Geraldo, Anjo, Matos, Almeida, Caramelo, Lopes-da-Silva, Paiva, Carvalho, Pires das Neves, Manadas and Gr{\~a}os.",
year = "2020",
month = jul,
day = "30",
doi = "10.3389/fcell.2020.00678",
language = "English",
volume = "8",
journal = "Frontiers in Cell and Developmental Biology",
issn = "2296-634X",
publisher = "Frontiers Media SA",
}