Abstract：
:Thick-filament sarcomere mutations are a common cause of hypertrophic cardiomyopathy (HCM), a disorder of heart muscle thickening associated with sudden cardiac death and heart failure, with unclear mechanisms. We engineered four isogenic induced pluripotent stem cell (iPSC) models of β-myosin heavy chain and myosin-binding protein C3 mutations, and studied iPSC-derived cardiomyocytes in cardiac microtissue assays that resemble cardiac architecture and biomechanics. All HCM mutations resulted in hypercontractility with prolonged relaxation kinetics in proportion to mutation pathogenicity, but not changes in calcium handling. RNA sequencing and expression studies of HCM models identified p53 activation, oxidative stress, and cytotoxicity induced by metabolic stress that can be reversed by p53 genetic ablation. Our findings implicate hypercontractility as a direct consequence of thick-filament mutations, irrespective of mutation localization, and the p53 pathway as a molecular marker of contraction stress and candidate therapeutic target for HCM patients.
journal_name
Stem Cell Reportsjournal_title
Stem cell reportsauthors
Cohn R,Thakar K,Lowe A,Ladha FA,Pettinato AM,Romano R,Meredith E,Chen YS,Atamanuk K,Huey BD,Hinson JTdoi
10.1016/j.stemcr.2018.11.015subject
Has Abstractpub_date
2019-01-08 00:00:00pages
71-83issue
1issn
2213-6711pii
S2213-6711(18)30483-1journal_volume
12pub_type
杂志文章abstract：:We describe the use of a characteristic blue fluorescence to identify and isolate pluripotent human embryonic stem cells and human-induced pluripotent stem cells. The blue fluorescence emission (450-500 nm) is readily observed by fluorescence microscopy and correlates with the expression of pluripotency markers (OCT4,...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2014.05.004
更新日期：2014-06-12 00:00:00
abstract：:Properties of cancer stem cells involved in drug resistance and relapse have significant effects on clinical outcome. Although tyrosine kinase inhibitors (TKIs) have dramatically improved survival of patients with chronic myeloid leukemia (CML), TKIs have not fully cured CML due to TKI-resistant CML stem cells. Moreov...
journal_title：Stem cell reports
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doi：10.1016/j.stemcr.2018.01.015
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abstract：:The small intestine plays an important role in the absorption and metabolism of oral drugs. In the current evaluation system, it is difficult to predict the precise absorption and metabolism of oral drugs. In this study, we generated small intestinal epithelial-like cells from human induced pluripotent stem cells (hiP...
journal_title：Stem cell reports
pub_type： 杂志文章
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abstract：:Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hold great promise for cardiac studies, but their structural and functional immaturity precludes their use as faithful models of adult myocardium. Here we describe engineered heart slices (EHS), preparations of decellularized porcine myocardium rep...
journal_title：Stem cell reports
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journal_title：Stem cell reports
pub_type： 杂志文章
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abstract：:We identified osteoclast defects in craniometaphyseal dysplasia (CMD) using an easy-to-use protocol for differentiating osteoclasts from human induced pluripotent stem cells (hiPSCs). CMD is a rare genetic bone disorder, characterized by life-long progressive thickening of craniofacial bones and abnormal shape of long...
journal_title：Stem cell reports
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abstract：:Deletion of caudal/cdx genes alters hox gene expression and causes defects in posterior tissues and hematopoiesis. Yet, the defects in hox gene expression only partially explain these phenotypes. To gain deeper insight into Cdx4 function, we performed chromatin immunoprecipitation sequencing (ChIP-seq) combined with g...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2013.10.001
更新日期：2013-11-07 00:00:00
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journal_title：Stem cell reports
pub_type： 杂志文章
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journal_title：Stem cell reports
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journal_title：Stem cell reports
pub_type： 杂志文章
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更新日期：2016-05-10 00:00:00
abstract：:The rigorous characterization of distinct induced pluripotent stem cells (iPSC) derived from multiple reprogramming technologies, somatic sources, and donors is required to understand potential sources of variability and downstream potential. To achieve this goal, the Progenitor Cell Biology Consortium performed compr...
journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2016.05.006
更新日期：2016-07-12 00:00:00
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journal_title：Stem cell reports
pub_type： 杂志文章
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journal_title：Stem cell reports
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journal_title：Stem cell reports
pub_type： 杂志文章
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journal_title：Stem cell reports
pub_type： 杂志文章
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journal_title：Stem cell reports
pub_type： 杂志文章
doi：10.1016/j.stemcr.2013.08.005
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journal_title：Stem cell reports
pub_type： 杂志文章
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更新日期：2021-01-06 00:00:00
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journal_title：Stem cell reports
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journal_title：Stem cell reports
pub_type： 杂志文章
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journal_title：Stem cell reports
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journal_title：Stem cell reports
pub_type： 杂志文章
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journal_title：Stem cell reports
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journal_title：Stem cell reports
pub_type： 杂志文章
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