دورية أكاديمية
Perlecan (HSPG2) promotes structural, contractile, and metabolic development of human cardiomyocytes.
| العنوان: | Perlecan (HSPG2) promotes structural, contractile, and metabolic development of human cardiomyocytes. |
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| المؤلفون: | Benjamin B Johnson, Marie-Victoire Cosson, Lorenza I Tsansizi, Terri L Holmes, Tegan Gilmore, Katherine Hampton, Ok-Ryul Song, Nguyen TN Vo, Aishah Nasir, Alzbeta Chabronova, Chris Denning, Mandy J Peffers, Catherine LR Merry, John Whitelock, Linda Troeberg, Stuart A Rushworth, Andreia S Bernardo, James GW Smith |
| سنة النشر: | 2024 |
| مصطلحات موضوعية: | Computational & Systems Biology, Model organisms, Tumour Biology, Signalling & Oncogenes, Gene Expression, Genetics & Genomics, Developmental Biology, Genome Integrity & Repair, Stem Cells, Chemical Biology & High Throughput, agrin, cardiac maturation, cardiomyocytes, CP: Cell biology, CP: Developmental biology, extracellular matrix, heparan sulfate proteoglycan, human pluripotent stem cells, hypertrophy, multinucleation, perlecan, perlecan mutation, Smith FC001157, HTS, CB, MAK-ack, Cano Ferrer, Xavier, Konstantinou, Georgios |
| الوصف: | Perlecan (HSPG2), a heparan sulfate proteoglycan similar to agrin, is key for extracellular matrix (ECM) maturation and stabilization. Although crucial for cardiac development, its role remains elusive. We show that perlecan expression increases as cardiomyocytes mature in vivo and during human pluripotent stem cell differentiation to cardiomyocytes (hPSC-CMs). Perlecan-haploinsuffient hPSCs (HSPG2+/-) differentiate efficiently, but late-stage CMs have structural, contractile, metabolic, and ECM gene dysregulation. In keeping with this, late-stage HSPG2+/- hPSC-CMs have immature features, including reduced ⍺-actinin expression and increased glycolytic metabolism and proliferation. Moreover, perlecan-haploinsuffient engineered heart tissues have reduced tissue thickness and force generation. Conversely, hPSC-CMs grown on a perlecan-peptide substrate are enlarged and display increased nucleation, typical of hypertrophic growth. Together, perlecan appears to play the opposite role of agrin, promoting cellular maturation rather than hyperplasia and proliferation. Perlecan signaling is likely mediated via its binding to the dystroglycan complex. Targeting perlecan-dependent signaling may help reverse the phenotypic switch common to heart failure. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| العلاقة: | https://figshare.com/articles/journal_contribution/Perlecan_HSPG2_promotes_structural_contractile_and_metabolic_development_of_human_cardiomyocytes_/24999020Test |
| DOI: | 10.25418/crick.24999020.v1 |
| الإتاحة: | https://doi.org/10.25418/crick.24999020.v1Test https://figshare.com/articles/journal_contribution/Perlecan_HSPG2_promotes_structural_contractile_and_metabolic_development_of_human_cardiomyocytes_/24999020Test |
| حقوق: | CC BY 4.0 |
| رقم الانضمام: | edsbas.19AB9B45 |
| قاعدة البيانات: | BASE |
| DOI: | 10.25418/crick.24999020.v1 |
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