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284: FES, VSMC behavior and pleiotropic vascular genes identified by integrative functional genomics

08 Feb 2026

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Solomon CU et al., Nat Commun ( - Integrative analysis in human VSMCs identifies pleiotropic genes including FES that regulate vascular remodeling; pooled CRISPR and mouse knockout show FES loss increases MMPs, atherosclerosis and blood pressure. Study Highlights:The study used a large human umbilical cord‑derived VSMC eQTL bank (n=1,486) combined with colocalization (eCAVIAR, SMR/HEIDI), ATAC‑seq, DNA methylation, H3K27ac HiChIP and pooled CRISPR‑Cas9 knockout screens to nominate likely causal genes for CAD, hypertension, stroke and AAA. Pooled CRISPR screens and siRNA validation in VSMCs highlighted BCAR1, CARF, SMARCA4 and FES as modulators of VSMC proliferation or migration, while FES knockdown increased MMP1/MMP3, reduced contractile markers and promoted migration by RNA‑seq and proteomics/phosphoproteomics. In vivo, Fes‑/-/Apoe‑/- mice had larger en face aortic lesion areas (8.34±2.54% vs 6.06±2.35%, P=0.013) and higher baseline systolic/diastolic blood pressure (104.4±6.7 vs 88.0±10.1 mmHg and 74.9±9.0 vs 58.8±8.9 mmHg, P=0.042). These results support FES as a pleiotropic, potentially druggable regulator of VSMC phenotype with functional effects on atherosclerosis and blood pressure. Conclusion:Integrative functional genomics implicates panels of likely causal and pleiotropic genes, including FES, that regulate VSMC behavior and whose loss promotes VSMC dedifferentiation, increased MMP production, larger atherosclerotic lesions and higher blood pressure. Music:Enjoy the music based on this article at the end of the episode. Reference:Solomon CU, McVey DG, Andreadi C, Peng G, Turner L, Song DSS, Zhang H, Lee DP, Karamanavi E, Yang W, Chu J, Chen R, Haworth KE, Anene-Nzelu CG, Li H, Denniff MJ, Li PY, Zhang Y, Huang X, Morris GE, Greer PA, Stringer EJ, Yu H, Foo RSY, Douglas G, Samani NJ, Webb TR, Ye S. Integrative functional genomics analysis identifies pleiotropic genes for vascular diseases. Nat Commun (2026). https://doi.org/10.1038/s41467-026-69273-8 License:This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) - https://creativecommons.org/licenses/by/4.0/ Support:Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 Official website https://basebybase.com On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics. Episode link: https://basebybase.castos.com/episodes/fes-vsmc-pleiotropic-genes

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13:00H | 21 DIC 2025 | Fin de Semana

01 Jan 1970

Fin de Semana

10:00H | 21 DIC 2025 | Fin de Semana

01 Jan 1970

Fin de Semana

12:00H | 20 DIC 2025 | Fin de Semana

01 Jan 1970

Fin de Semana

2ª PARTE | 06 ENE 2026 | EL PARTIDAZO DE COPE

01 Jan 1970

El Partidazo de COPE

3ª PARTE | 22 ENE 2026 | EL PARTIDAZO DE COPE

01 Jan 1970

El Partidazo de COPE

3ª PARTE | 04 MAR 2026 | EL PARTIDAZO DE COPE

01 Jan 1970

El Partidazo de COPE

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284: FES, VSMC behavior and pleiotropic vascular genes identified by integrative functional genomics

This episode hasn't been transcribed yet

Other recent transcribed episodes

13:00H | 21 DIC 2025 | Fin de Semana

10:00H | 21 DIC 2025 | Fin de Semana

12:00H | 20 DIC 2025 | Fin de Semana

2ª PARTE | 06 ENE 2026 | EL PARTIDAZO DE COPE

3ª PARTE | 22 ENE 2026 | EL PARTIDAZO DE COPE

3ª PARTE | 04 MAR 2026 | EL PARTIDAZO DE COPE

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