Transcriptional Targets of TWIST1 in Human Mesenchymal Stem/Stromal Cells Mechanistically Link Stem/Progenitor and Paracrine Functions.
Autor: | Haga CL; The Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technology, Department of Molecular Medicine, Jupiter, FL, USA., Booker CN; The Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technology, Department of Molecular Medicine, Jupiter, FL, USA., Carvalho A; The Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technology, Department of Molecular Medicine, Jupiter, FL, USA., Boregowda SV; The Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technology, Department of Molecular Medicine, Jupiter, FL, USA., Phinney DG; The Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technology, Department of Molecular Medicine, Jupiter, FL, USA. |
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Jazyk: | angličtina |
Zdroj: | Stem cells (Dayton, Ohio) [Stem Cells] 2023 Dec 14; Vol. 41 (12), pp. 1185-1200. |
DOI: | 10.1093/stmcls/sxad070 |
Abstrakt: | Despite extensive clinical testing, mesenchymal stem/stromal cell (MSC)-based therapies continue to underperform with respect to efficacy, which reflects the paucity of biomarkers that predict potency prior to patient administration. Previously, we reported that TWIST1 predicts inter-donor differences in MSC quality attributes that confer potency. To define the full spectrum of TWIST1 activity in MSCs, the present work employed integrated omics-based profiling to identify a high-confidence set of TWIST1 targets, which mapped to cellular processes related to ECM structure/organization, skeletal and circulatory system development, interferon gamma signaling, and inflammation. These targets are implicated in contributing to both stem/progenitor and paracrine activities of MSCs indicating these processes are linked mechanistically in a TWIST1-dependent manner. Targets implicated in extracellular matrix dynamics further implicate TWIST1 in modulating cellular responses to niche remodeling. Novel TWIST1-regulated genes identified herein may be prioritized for future mechanistic and functional studies. (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.) |
Databáze: | MEDLINE |
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