{"id":531,"date":"2020-09-18T09:04:50","date_gmt":"2020-09-18T12:04:50","guid":{"rendered":"http:\/\/sites.icgbio.ru\/zakianlab-ipsccollection\/?p=531"},"modified":"2021-05-26T17:43:36","modified_gmt":"2021-05-26T20:43:36","slug":"hypertrophic-cardiomyopathy","status":"publish","type":"post","link":"https:\/\/sites.icgbio.ru\/zakianlab-ipsccollection\/hypertrophic-cardiomyopathy\/","title":{"rendered":"Hypertrophic cardiomyopathy"},"content":{"rendered":"\t\t
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Hypertrophic cardiomyopathy (HCM) is one of the most common cardiovascular diseases and is characterized by abnormal thickness of left ventricular wall and interventricular septum, diastolic dysfunction, progressive heart failure, and a high risk of arrhythmias and sudden death. Inherited form of the disease is caused predominately by mutations in genes encoding for sarcomere-associated proteins. However, no effective methods to prevent HCM progression have been developed so far. Patient-specific iPSC-derived cardiomyocytes can afford new opportunities in unraveling HCM pathogenic mechanisms. Using episomal vectors, we generated iPSC lines from peripheral blood mononuclear cells of two HCM patients carrying mutations with unknown clinical significance in disease-associated genes \u2013 p.M659I in MYH7 ( https:\/\/hpscreg.eu\/cell-line\/ICGi019-A<\/a> , https:\/\/hpscreg.eu\/cell-line\/ICGi019-B<\/a> ) and p.N515del in MYBPC3 ( https:\/\/hpscreg.eu\/cell-line\/ICGi029-A<\/a> ).<\/p>

The iPSC lines can become a tool for clarifying the roles of the mutations in HCM pathogenesis, for studying molecular mechanisms of the disease, and for testing drugs and new therapy methods. In addition, we generated an iPSC line from a patient carrying a heterozygous p.E510Q mutation in HADHA encoding for long-chain 3-hydroxyacyl-CoA dehydrogenase that participates in mitochondrial fatty acid \u03b2-oxidation ( https:\/\/hpscreg.eu\/cell-line\/ICGi028-A<\/a> ). This iPSC line can be used for generating cardiomyocytes that may represent an HCM case caused by metabolic impairments.<\/p>\t\t\t\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t

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Characterization of the ICGi028-A iPSC line. A. Morphology of the iPSC line (Scale bar \u2013 100 \u03bcm). B. Expression of pluripotency markers - OCT4, NANOG, TRA-1\u201360, SSEA4 shown using immunofluorescent staining (Scale bar \u2013 50 \u03bcm). C. Analysis of pluripotency genes (OCT4, NANOG, SOX2) expression in the ICGi028- A iPSC line compared to the parental MNCs by RT-qPCR. HUES9, human embryonic stem cell line used as a control. D. Karyotype of the iPSC line. E. Spontaneous in vitro differentiation of the ICGi028-A iPSC line in embryoid bodies. Immunofluorescent staining for TUBB3 and NF200 (ectoderm), \u03b1SMA and collagen type I (mesoderm), CK18 and HNF3\u03b2\/FOXA2 (endoderm) (Scale bar \u2013 50 \u03bcm). F. Patient-specific mutation verification by Sanger sequencing of exon 15 of HADHA in the ICGi028-A iPSC line and healthy donor (WT). The heterozygous p.E510Q (c.1528G>C) mutation in HADHA is indicated by arrow.<\/figcaption>\n\t\t\t\t\t\t\t\t\t\t<\/figure>\n\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t
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Characterization of the ICGi029-A iPSC line. A. Morphology of the iPSC colonies (Scale bar \u2013 100 \u03bcm). B. Immunofluorescent staining for pluripotency markers - OCT4, NANOG, TRA-1\u201360, SSEA4 (Scale bar \u2013 50 \u03bcm). C. Analysis of pluripotency genes (OCT4, NANOG, SOX2) expression in the iPSC line relative to parental MNCs by RT-qPCR. Human embryonic stem cell line, HUES9, was used as a control. D. Karyotype of the iPSC line. E. Immunofluorescent staining for three germ layer markers, TUBB3 and NF200 (ectoderm), \u03b1SMA and collagen type I (mesoderm), CK18 and HNF3\u03b2\/FOXA2 (endoderm), after spontaneous in vitro differentiation in embryoid bodies (Scale bar \u2013 50 \u03bcm). F. Mutation analysis. Sanger sequencing of exon 17 of MYBPC3 in the ICGi029-A iPSC line and healthy donor (WT). Boundaries of the heterozygous trinucleotide (c.1543_1545delAAC, p.N515del) deletion in MYBPC3 are indicated by arrows.<\/figcaption>\n\t\t\t\t\t\t\t\t\t\t<\/figure>\n\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t
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Hypertrophic cardiomyopathy (HCM) is one of the most common cardiovascular diseases and is characterized by abnormal thickness of left ventricular wall and interventricular septum, diastolic dysfunction, progressive heart failure, and a high risk of arrhythmias and sudden death. Inherited form of the disease is caused predominately by mutations in genes encoding for sarcomere-associated proteins. However, no effective methods to prevent HCM progression have been developed so far. Patient-specific iPSC-derived cardiomyocytes can afford new opportunities in unraveling HCM pathogenic mechanisms. Using episomal vectors, we generated iPSC lines from peripheral blood mononuclear cells of two HCM patients carrying mutations with unknown clinical significance in disease-associated genes \u2013 p.M659I in MYH7 ( https:\/\/hpscreg.eu\/cell-line\/ICGi019-A<\/a> , https:\/\/hpscreg.eu\/cell-line\/ICGi019-B<\/a> ) and p.N515del in MYBPC3 ( https:\/\/hpscreg.eu\/cell-line\/ICGi029-A<\/a> ).<\/p>

The iPSC lines can become a tool for clarifying the roles of the mutations in HCM pathogenesis, for studying molecular mechanisms of the disease, and for testing drugs and new therapy methods. In addition, we generated an iPSC line from a patient carrying a heterozygous p.E510Q mutation in HADHA encoding for long-chain 3-hydroxyacyl-CoA dehydrogenase that participates in mitochondrial fatty acid \u03b2-oxidation ( https:\/\/hpscreg.eu\/cell-line\/ICGi028-A<\/a> ). This iPSC line can be used for generating cardiomyocytes that may represent an HCM case caused by metabolic impairments.<\/p>\t\t\t\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t\t\t\t\t\t<\/div>\n\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t","protected":false},"excerpt":{"rendered":"

Hypertrophic cardiomyopathy (HCM) is one of the most common cardiovascular diseases and is characterized by abnormal thickness of left ventricular wall and interventricular septum, diastolic dysfunction, progressive heart failure, and a high risk of arrhythmias and sudden death. Inherited form of the disease is caused predominately by mutations in genes encoding for sarcomere-associated proteins. However, […]<\/p>\n","protected":false},"author":31,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"elementor_header_footer","format":"standard","meta":[],"categories":[2],"tags":[59,58],"_links":{"self":[{"href":"https:\/\/sites.icgbio.ru\/zakianlab-ipsccollection\/wp-json\/wp\/v2\/posts\/531"}],"collection":[{"href":"https:\/\/sites.icgbio.ru\/zakianlab-ipsccollection\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/sites.icgbio.ru\/zakianlab-ipsccollection\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/sites.icgbio.ru\/zakianlab-ipsccollection\/wp-json\/wp\/v2\/users\/31"}],"replies":[{"embeddable":true,"href":"https:\/\/sites.icgbio.ru\/zakianlab-ipsccollection\/wp-json\/wp\/v2\/comments?post=531"}],"version-history":[{"count":27,"href":"https:\/\/sites.icgbio.ru\/zakianlab-ipsccollection\/wp-json\/wp\/v2\/posts\/531\/revisions"}],"predecessor-version":[{"id":2314,"href":"https:\/\/sites.icgbio.ru\/zakianlab-ipsccollection\/wp-json\/wp\/v2\/posts\/531\/revisions\/2314"}],"wp:attachment":[{"href":"https:\/\/sites.icgbio.ru\/zakianlab-ipsccollection\/wp-json\/wp\/v2\/media?parent=531"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sites.icgbio.ru\/zakianlab-ipsccollection\/wp-json\/wp\/v2\/categories?post=531"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sites.icgbio.ru\/zakianlab-ipsccollection\/wp-json\/wp\/v2\/tags?post=531"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}