{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T12:35:27Z","timestamp":1792672527827,"version":"4.5.0"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2019,4,12]]},"abstract":"<jats:sec>\n                    <jats:title>\n                      <jats:underline>Rationale:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>Human induced pluripotent stem cell\u2013derived cardiomyocytes (hiPSC-CMs) in combination with CRISPR\/Cas9 genome editing provide unparalleled opportunities to study cardiac biology and disease. However, sarcomeres, the fundamental units of myocyte contraction, are immature and nonlinear in hiPSC-CMs, which technically challenge accurate functional interrogation of contractile parameters in beating cells. Furthermore, existing analysis methods are relatively low-throughput, indirectly assess contractility, or only assess well-aligned sarcomeres found in mature cardiac tissues.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Objective:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>We aimed to develop an analysis platform that directly, rapidly, and automatically tracks sarcomeres in beating cardiomyocytes. The platform should assess sarcomere content, contraction and relaxation parameters, and beat rate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Methods and Results:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>\n                      We developed SarcTrack, a MatLab software that monitors fluorescently tagged sarcomeres in hiPSC-CMs. The algorithm determines sarcomere content, sarcomere length, and returns rates of sarcomere contraction and relaxation. By rapid measurement of hundreds of sarcomeres in each hiPSC-CM, SarcTrack provides large data sets for robust statistical analyses of multiple contractile parameters. We validated SarcTrack by analyzing drug-treated hiPSC-CMs, confirming the contractility effects of compounds that directly activate (CK-1827452) or inhibit (MYK-461) myosin molecules or indirectly alter contractility (verapamil and propranolol). SarcTrack analysis of hiPSC-CMs carrying a heterozygous truncation variant in the myosin-binding protein C (\n                      <jats:italic>MYBPC3<\/jats:italic>\n                      ) gene, which causes hypertrophic cardiomyopathy, recapitulated seminal disease phenotypes including cardiac hypercontractility and diminished relaxation, abnormalities that normalized with MYK-461 treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Conclusions:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>SarcTrack provides a direct and efficient method to quantitatively assess sarcomere function. By improving existing contractility analysis methods and overcoming technical challenges associated with functional evaluation of hiPSC-CMs, SarcTrack enhances translational prospects for sarcomere-regulating therapeutics and accelerates interrogation of human cardiac genetic variants.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.118.314505","type":"journal-article","created":{"date-parts":[[2019,1,31]],"date-time":"2019-01-31T05:05:14Z","timestamp":1548911114000},"page":"1172-1183","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":124,"title":["SarcTrack"],"prefix":"10.1161","volume":"124","author":[{"given":"Christopher N.","family":"Toepfer","sequence":"first","affiliation":[{"name":"From the Department of Genetics (C.N.T., A.S., A.C.G., M.N., J.A.L.W., R.A., M.S., J.R., O.P., J.G.S., C.E.S.), Harvard Medical School, Boston, MA"},{"name":"Cardiovascular Medicine, Radcliffe Department of Medicine (C.N.T.), University of Oxford, United Kingdom"},{"name":"Wellcome Centre for Human Genetics (C.N.T.), University of Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun","family":"Sharma","sequence":"additional","affiliation":[{"name":"From the Department of Genetics (C.N.T., A.S., A.C.G., M.N., J.A.L.W., R.A., M.S., J.R., O.P., J.G.S., C.E.S.), Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo","family":"Cicconet","sequence":"additional","affiliation":[{"name":"Image and Data Analysis Core (M.C.), Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda C.","family":"Garfinkel","sequence":"additional","affiliation":[{"name":"From the Department of Genetics (C.N.T., A.S., A.C.G., M.N., J.A.L.W., R.A., M.S., J.R., O.P., J.G.S., C.E.S.), Harvard Medical School, Boston, 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MA"},{"name":"Department of Pathology (J.R., O.P.), Brigham and Women\u2019s Hospital, Boston, MA"},{"name":"Harvard Stem Cell Institute, Boston, MA (J.R., O.P.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jourdan","family":"Ewoldt","sequence":"additional","affiliation":[{"name":"Biomedical Engineering, Boston University, MA (J.E., A.C., C.S.C.)"},{"name":"The Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA (J.E., A.C., C.S.C.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Pourqui\u00e9","sequence":"additional","affiliation":[{"name":"From the Department of Genetics (C.N.T., A.S., A.C.G., M.N., J.A.L.W., R.A., M.S., J.R., O.P., J.G.S., C.E.S.), Harvard Medical School, Boston, MA"},{"name":"Department of Pathology (J.R., O.P.), Brigham and Women\u2019s Hospital, Boston, MA"},{"name":"Harvard Stem Cell Institute, Boston, MA (J.R., 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