{"id":"https://openalex.org/W7222877381","doi":"https://doi.org/10.64898/2026.10.11.758388","title":"Human iPSC-Derived Cardiomyocytes Maladaptively Remodel to Cyclic Stretch in Hypoplastic Left Heart Syndrome","display_name":"Human iPSC-Derived Cardiomyocytes Maladaptively Remodel to Cyclic Stretch in Hypoplastic Left Heart Syndrome","publication_year":2026,"publication_date":"2026-10-17","ids":{"openalex":"https://openalex.org/W7222877381","doi":"https://doi.org/10.64898/2026.10.11.758388"},"language":"en","primary_location":{"id":"doi:10.64898/2026.10.11.758388","doi":"https://doi.org/10.64898/2026.10.11.758388","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.10.11.758388","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/10/17/2026.10.11.758388.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.biorxiv.org/content/biorxiv/early/2026/10/17/2026.10.11.758388.full.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5159009201","display_name":"Riya Singh Verma","orcid":"https://orcid.org/0000-0003-1795-1497","observed_orcids":["https://orcid.org/0000-0003-1795-1497"]},"institutions":[{"id":"https://openalex.org/I1174212","display_name":"University of Southern California","ror":"https://ror.org/03taz7m60","country_code":"US","type":"education","lineage":["https://openalex.org/I1174212"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Riya S. Verma","raw_affiliation_strings":["Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA 90033, USA"],"raw_orcid":"https://orcid.org/0000-0003-1795-1497","affiliations":[{"raw_affiliation_string":"Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA 90033, USA","institution_ids":["https://openalex.org/I1174212"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5159001431","display_name":"Ivy Zhang","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1174212","display_name":"University of Southern California","ror":"https://ror.org/03taz7m60","country_code":"US","type":"education","lineage":["https://openalex.org/I1174212"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Ivy Zhang","raw_affiliation_strings":["Dornsife College of Letters, Arts, and Sciences, University of Southern California, Los Angeles, CA 90089, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Dornsife College of Letters, Arts, and Sciences, University of Southern California, Los Angeles, CA 90089, USA","institution_ids":["https://openalex.org/I1174212"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5113381381","display_name":"Xunyang Chen","orcid":"https://orcid.org/0009-0000-7612-7209","observed_orcids":["https://orcid.org/0009-0000-7612-7209"]},"institutions":[{"id":"https://openalex.org/I1174212","display_name":"University of Southern California","ror":"https://ror.org/03taz7m60","country_code":"US","type":"education","lineage":["https://openalex.org/I1174212"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Xunyang Chen","raw_affiliation_strings":["Alfred E. Mann Department of Biomedical Engineering, USC Viterbi School of Engineering, University of Southern California, Los Angeles, CA 90089, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Alfred E. Mann Department of Biomedical Engineering, USC Viterbi School of Engineering, University of Southern California, Los Angeles, CA 90089, USA","institution_ids":["https://openalex.org/I1174212"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5159017827","display_name":"Maddison S Pierce","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1174212","display_name":"University of Southern California","ror":"https://ror.org/03taz7m60","country_code":"US","type":"education","lineage":["https://openalex.org/I1174212"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Maddison S. Pierce","raw_affiliation_strings":["Alfred E. Mann Department of Biomedical Engineering, USC Viterbi School of Engineering, University of Southern California, Los Angeles, CA 90089, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Alfred E. Mann Department of Biomedical Engineering, USC Viterbi School of Engineering, University of Southern California, Los Angeles, CA 90089, USA","institution_ids":["https://openalex.org/I1174212"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5159004645","display_name":"S. Ram Kumar","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I59130452","display_name":"University of Nebraska Medical Center","ror":"https://ror.org/00thqtb16","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I59130452"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Ram Kumar Subramanyan","raw_affiliation_strings":["Division of Pediatric Cardiothoracic Surgery, University of Nebraska Medical Center, Omaha, NE 68198-2315, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Pediatric Cardiothoracic Surgery, University of Nebraska Medical Center, Omaha, NE 68198-2315, USA","institution_ids":["https://openalex.org/I59130452"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5077454813","display_name":"Megan Laura McCain","orcid":"https://orcid.org/0000-0003-1908-6783","observed_orcids":["https://orcid.org/0000-0003-1908-6783"]},"institutions":[{"id":"https://openalex.org/I1174212","display_name":"University of Southern California","ror":"https://ror.org/03taz7m60","country_code":"US","type":"education","lineage":["https://openalex.org/I1174212"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Megan L. McCain","raw_affiliation_strings":["Alfred E. Mann Department of Biomedical Engineering, USC Viterbi School of Engineering, University of Southern California, Los Angeles, CA 90089, USA","Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA 90033, USA"],"raw_orcid":"https://orcid.org/0000-0003-1908-6783","affiliations":[{"raw_affiliation_string":"Alfred E. Mann Department of Biomedical Engineering, USC Viterbi School of Engineering, University of Southern California, Los Angeles, CA 90089, USA","institution_ids":["https://openalex.org/I1174212"]},{"raw_affiliation_string":"Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA 90033, USA","institution_ids":["https://openalex.org/I1174212"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5077454813"],"corresponding_institution_ids":["https://openalex.org/I1174212"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11677","display_name":"Congenital heart defects research","score":0.5800999999046326,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T11677","display_name":"Congenital heart defects research","score":0.5800999999046326,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10505","display_name":"Pluripotent Stem Cells Research","score":0.12229999899864197,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10217","display_name":"Cardiac electrophysiology and arrhythmias","score":0.053599998354911804,"subfield":{"id":"https://openalex.org/subfields/2705","display_name":"Cardiology and Cardiovascular Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/hypoplastic-left-heart-syndrome","display_name":"hypoplastic left heart syndrome","score":0.9869999885559082},{"id":"https://openalex.org/keywords/induced-pluripotent-stem-cell-derived-cardiomyocytes","display_name":"iPSC-derived cardiomyocytes","score":0.9890000224113464},{"id":"https://openalex.org/keywords/cyclic-stretch","display_name":"cyclic strain","score":0.9409999847412109},{"id":"https://openalex.org/keywords/mechanoadaptation","display_name":"mechanical adaptation","score":0.984000027179718},{"id":"https://openalex.org/keywords/calcium-transients","display_name":"calcium transients","score":0.8830000162124634},{"id":"https://openalex.org/keywords/sarcomere-organization","display_name":"sarcomere organization","score":0.8799999952316284},{"id":"https://openalex.org/keywords/calcium-handling","display_name":"calcium handling","score":0.5600000023841858},{"id":"https://openalex.org/keywords/inflammatory-signaling-pathways","display_name":"inflammatory signaling","score":0.859000027179718},{"id":"https://openalex.org/keywords/congenital-heart-disease","display_name":"congenital heart disease","score":0.6349999904632568},{"id":"https://openalex.org/keywords/right-ventricle","display_name":"right ventricle","score":0.6200000047683716}],"concepts":[{"id":"https://openalex.org/C2779545397","wikidata":"https://www.wikidata.org/wiki/Q1641399","display_name":"Hypoplastic left heart syndrome","level":3,"score":0.9293000102043152},{"id":"https://openalex.org/C2778921608","wikidata":"https://www.wikidata.org/wiki/Q2002035","display_name":"Ventricle","level":2,"score":0.7598000168800354},{"id":"https://openalex.org/C68731436","wikidata":"https://www.wikidata.org/wiki/Q1337087","display_name":"Sarcomere","level":3,"score":0.5623000264167786},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.5461000204086304},{"id":"https://openalex.org/C519063684","wikidata":"https://www.wikidata.org/wiki/Q706","display_name":"Calcium","level":2,"score":0.517799973487854},{"id":"https://openalex.org/C164705383","wikidata":"https://www.wikidata.org/wiki/Q10379","display_name":"Cardiology","level":1,"score":0.5123999714851379},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.4553000032901764},{"id":"https://openalex.org/C107459253","wikidata":"https://www.wikidata.org/wiki/Q674925","display_name":"Induced pluripotent stem cell","level":4,"score":0.36079999804496765},{"id":"https://openalex.org/C72859922","wikidata":"https://www.wikidata.org/wiki/Q11068","display_name":"Circulatory system","level":2,"score":0.31859999895095825},{"id":"https://openalex.org/C162317418","wikidata":"https://www.wikidata.org/wiki/Q252857","display_name":"Transcriptome","level":4,"score":0.3154999911785126},{"id":"https://openalex.org/C2778198053","wikidata":"https://www.wikidata.org/wiki/Q181754","display_name":"Heart failure","level":2,"score":0.301800012588501},{"id":"https://openalex.org/C39133596","wikidata":"https://www.wikidata.org/wiki/Q5165683","display_name":"Contractility","level":2,"score":0.2775999903678894},{"id":"https://openalex.org/C105702510","wikidata":"https://www.wikidata.org/wiki/Q514","display_name":"Anatomy","level":1,"score":0.26159998774528503},{"id":"https://openalex.org/C2780327212","wikidata":"https://www.wikidata.org/wiki/Q1568160","display_name":"Hypoplasia","level":2,"score":0.25540000200271606},{"id":"https://openalex.org/C178853913","wikidata":"https://www.wikidata.org/wiki/Q1642137","display_name":"Hemodynamics","level":2,"score":0.2531000077724457},{"id":"https://openalex.org/C207200792","wikidata":"https://www.wikidata.org/wiki/Q428914","display_name":"Myocyte","level":2,"score":0.2524000108242035}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.64898/2026.10.11.758388","doi":"https://doi.org/10.64898/2026.10.11.758388","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.10.11.758388","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/10/17/2026.10.11.758388.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.64898/2026.10.11.758388","doi":"https://doi.org/10.64898/2026.10.11.758388","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.10.11.758388","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/10/17/2026.10.11.758388.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.98580002784729}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7222877381.pdf","grobid_xml":"https://content.openalex.org/works/W7222877381.grobid-xml"},"referenced_works_count":61,"referenced_works":["https://openalex.org/W611730944","https://openalex.org/W1591850964","https://openalex.org/W1979955583","https://openalex.org/W1991014863","https://openalex.org/W2008485310","https://openalex.org/W2010216650","https://openalex.org/W2024935562","https://openalex.org/W2025004005","https://openalex.org/W2041570625","https://openalex.org/W2052763120","https://openalex.org/W2054898931","https://openalex.org/W2056483214","https://openalex.org/W2062182733","https://openalex.org/W2064654522","https://openalex.org/W2076700858","https://openalex.org/W2077411280","https://openalex.org/W2079176005","https://openalex.org/W2102594196","https://openalex.org/W2108230283","https://openalex.org/W2110096767","https://openalex.org/W2115147488","https://openalex.org/W2119706727","https://openalex.org/W2141336992","https://openalex.org/W2147262751","https://openalex.org/W2408609101","https://openalex.org/W2528344316","https://openalex.org/W2615483894","https://openalex.org/W2619470987","https://openalex.org/W2624797807","https://openalex.org/W2743410506","https://openalex.org/W2765584642","https://openalex.org/W2781096653","https://openalex.org/W2787234767","https://openalex.org/W2789055329","https://openalex.org/W2803337845","https://openalex.org/W2806554262","https://openalex.org/W2885240581","https://openalex.org/W2899037189","https://openalex.org/W2955245401","https://openalex.org/W2975681149","https://openalex.org/W3004299218","https://openalex.org/W3005783703","https://openalex.org/W3027216380","https://openalex.org/W3034163767","https://openalex.org/W3046454618","https://openalex.org/W3049056316","https://openalex.org/W3088401235","https://openalex.org/W3092883939","https://openalex.org/W3176992750","https://openalex.org/W3214891507","https://openalex.org/W4221001022","https://openalex.org/W4223587854","https://openalex.org/W4224081138","https://openalex.org/W4283837698","https://openalex.org/W4288034201","https://openalex.org/W4391041707","https://openalex.org/W4403038646","https://openalex.org/W4411332086","https://openalex.org/W4413020914","https://openalex.org/W4417080071","https://openalex.org/W7128498580"],"related_works":["https://openalex.org/W2075552622","https://openalex.org/W2889306919","https://openalex.org/W4387621100","https://openalex.org/W6991282102","https://openalex.org/W3034163767","https://openalex.org/W4414937237","https://openalex.org/W4416986405","https://openalex.org/W6945972977","https://openalex.org/W4398167064","https://openalex.org/W4403246862"],"abstract_inverted_index":{"Abstract":[0],"Background":[1],"Hypoplastic":[2],"Left":[3],"Heart":[4],"Syndrome":[5],"(HLHS)":[6],"is":[7],"a":[8,234,284,318],"severe":[9],"congenital":[10],"heart":[11,43],"defect":[12],"characterized":[13],"by":[14],"underdevelopment":[15],"of":[16,61,86,164,240,243,253,280,305],"left-sided":[17],"cardiac":[18],"structures,":[19],"requiring":[20],"staged":[21],"surgical":[22],"palliation":[23],"that":[24,69,76,249],"establishes":[25],"the":[26,30,48,54,59,67,82,87],"right":[27],"ventricle":[28,32,323],"as":[29,317],"single":[31,55,322],"maintaining":[33],"systemic":[34],"circulation.":[35],"After":[36],"surgery,":[37],"patients":[38,104,131,295],"remain":[39],"highly":[40],"susceptible":[41],"to":[42,47,93,116,145,191,218,222,257,266,276,299,321],"failure,":[44],"possibly":[45],"due":[46],"increased":[49],"hemodynamic":[50],"load":[51],"imposed":[52],"on":[53],"surviving":[56],"ventricle.":[57,88],"Because":[58],"etiology":[60],"HLHS":[62,106,130,199,205,244,254,274,294,337],"remains":[63],"poorly":[64],"understood,":[65],"elucidating":[66],"mechanisms":[68],"drive":[70],"ventricular":[71],"dysfunction":[72],"requires":[73],"model":[74],"systems":[75],"capture":[77],"both":[78],"patient-specific":[79],"genetics":[80],"and":[81,113,126,140,176,198,213,261,308,325,330],"dynamic":[83],"mechanical":[84],"environment":[85],"Thus,":[89],"our":[90],"objective":[91],"was":[92,157,189],"compare":[94],"how":[95],"induced":[96,273],"pluripotent":[97],"stem":[98],"cell":[99],"(iPSC)-derived":[100],"cardiomyocytes":[101],"(iPSC-CMs)":[102],"from":[103,108,122,128,293],"with":[105,230],"differ":[107],"control":[109,197,225,269,289],"in":[110,114,159,174,196,210,237,264,288],"static":[111,160,175,203],"culture":[112],"response":[115,221,235,265,285],"cyclic":[117,146,223,300],"stretch.":[118],"Methods":[119],"Control":[120],"iPSCs":[121,127],"two":[123],"unaffected":[124],"donors":[125],"four":[129,241,251],"were":[132,179],"differentiated":[133],"into":[134,137],"iPSC-CMs,":[135],"engineered":[136],"aligned":[138],"tissues,":[139],"cultured":[141],"statically":[142],"or":[143],"exposed":[144],"20%":[147],"uniaxial":[148],"stretch":[149],"at":[150,169],"1":[151,170],"Hz":[152,171],"for":[153,333,336],"48h.":[154],"Sarcomere":[155],"organization":[156,212],"quantified":[158],"tissues":[161,178],"using":[162,181],"images":[163],"immunostained":[165],"\u03b1-actinin.":[166],"Calcium":[167],"transients":[168,229,307],"pacing":[172],"frequency":[173],"stretched":[177],"evaluated":[180],"Fluo-4":[182],"calcium":[183,214,228,259,306],"indicator":[184],"dye.":[185],"Bulk":[186],"RNA":[187],"sequencing":[188],"performed":[190],"evaluate":[192],"stretch-induced":[193],"transcriptomic":[194],"changes":[195],"iPSC-CMs.":[200,245,270,290],"Results":[201],"In":[202,220],"culture,":[204],"iPSC-CMs":[206,226,255,275,292],"had":[207],"modest":[208],"defects":[209],"sarcomere":[211],"transient":[215],"morphology":[216],"compared":[217],"control.":[219],"stretch,":[224,267,301],"exhibited":[227],"quicker":[231],"rise":[232],"time,":[233],"observed":[236,287],"only":[238],"one":[239],"lines":[242,252],"Transcriptomic":[246],"analysis":[247],"revealed":[248],"all":[250],"failed":[256],"upregulate":[258],"handling":[260],"sarcomere-associated":[262],"genes":[263],"unlike":[268],"Stretch":[271],"also":[272],"exhibit":[277],"pronounced":[278],"activation":[279],"inflammatory":[281,310],"signaling":[282],"pathways,":[283],"not":[286],"Conclusions":[291],"demonstrate":[296],"aberrant":[297],"responses":[298],"including":[302],"blunted":[303],"adaptation":[304],"heightened":[309],"signaling.":[311],"These":[312],"findings":[313],"implicate":[314],"defective":[315],"mechanoadaptation":[316],"potential":[319,327],"contributor":[320],"failure":[324],"identify":[326],"candidate":[328],"biomarkers":[329],"new":[331],"opportunities":[332],"therapeutic":[334],"interventions":[335],"patients.":[338]},"counts_by_year":[],"updated_date":"2026-11-08T12:12:28.789561","created_date":"2026-10-19T00:00:00"}
