{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T20:56:07Z","timestamp":1768251367129,"version":"3.49.0"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"20","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2020,10,20]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">To understand the intrinsic cardiac developmental and functional abnormalities in pulmonary atresia with intact ventricular septum (PAIVS) free from effects secondary to anatomic defects, we performed and compared single\u2010cell transcriptomic and phenotypic analyses of patient\u2010 and healthy subject\u2013derived human\u2010induced pluripotent stem cell\u2013derived cardiomyocytes (hiPSC\u2010CMs) and engineered tissue models.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">We derived hiPSC lines from 3 patients with PAIVS and 3 healthy subjects and differentiated them into hiPSC\u2010CMs, which were then bioengineered into the human cardiac anisotropic sheet and human cardiac tissue strip custom\u2010designed for electrophysiological and contractile assessments, respectively. Single\u2010cell RNA sequencing (scRNA\u2010seq) of hiPSC\u2010CMs, human cardiac anisotropic sheet, and human cardiac tissue strip was performed to examine the transcriptomic basis for any phenotypic abnormalities using pseudotime and differential expression analyses. Through pseudotime analysis, we demonstrated that bioengineered tissue constructs provide pro\u2010maturational cues to hiPSC\u2010CMs, although the maturation and development were attenuated in PAIVS hiPSC\u2010CMs. Furthermore, reduced contractility and prolonged contractile kinetics were observed with PAIVS human cardiac tissue strips. Consistently, single\u2010cell RNA sequencing of PAIVS human cardiac tissue strips and hiPSC\u2010CMs exhibited diminished expression of cardiac contractile apparatus genes. By contrast, electrophysiological aberrancies were absent in PAIVS human cardiac anisotropic sheets.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Our findings were the first to reveal intrinsic abnormalities of cardiomyocyte development and function in PAIVS free from secondary effects. We conclude that hiPSC\u2010derived engineered tissues offer a unique method for studying primary cardiac abnormalities and uncovering pathogenic mechanisms that underlie sporadic congenital heart diseases.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.120.016528","type":"journal-article","created":{"date-parts":[[2020,10,16]],"date-time":"2020-10-16T08:59:33Z","timestamp":1602838773000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":39,"title":["Single\u2010Cell Transcriptomics of Engineered Cardiac Tissues From Patient\u2010Specific Induced Pluripotent Stem Cell\u2013Derived Cardiomyocytes Reveals Abnormal Developmental Trajectory and Intrinsic Contractile Defects in Hypoplastic Right Heart Syndrome"],"prefix":"10.1161","volume":"9","author":[{"given":"Yin\u2010Yu","family":"Lam","sequence":"first","affiliation":[{"name":"Department of Paediatrics and Adolescent Medicine Li Ka Shing Faculty of Medicine The 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