{"id":6374,"date":"2023-02-17T06:49:00","date_gmt":"2023-02-17T06:49:00","guid":{"rendered":"https:\/\/beta.nanion.de\/resource_library\/2020-advancing-physiological-maturation-in-human-induced-pluripotent-stem-cell%e2%80%90derived-cardiac-muscle-by-gene-editing-an-inducible-adult-troponin-isoform-switch\/"},"modified":"2023-02-17T06:49:00","modified_gmt":"2023-02-17T06:49:00","slug":"2020-advancing-physiological-maturation-in-human-induced-pluripotent-stem-cell%e2%80%90derived-cardiac-muscle-by-gene-editing-an-inducible-adult-troponin-isoform-switch","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/zh-hans\/resource_library\/2020-advancing-physiological-maturation-in-human-induced-pluripotent-stem-cell%e2%80%90derived-cardiac-muscle-by-gene-editing-an-inducible-adult-troponin-isoform-switch\/","title":{"rendered":"2020 &#8211; Advancing physiological maturation in human induced pluripotent stem cell\u2010derived cardiac muscle by gene editing an inducible adult troponin isoform switch"},"content":{"rendered":"<p>Advancing maturation of stem cell\u2010derived cardiac muscle represents a major barrier to progress in cardiac regenerative medicine. Cardiac muscle maturation involves a myriad of gene, protein, and cell\u2010based transitions, spanning across all aspects of cardiac muscle form and function. We focused here on a key developmentally controlled transition in the cardiac sarcomere, the functional unit of the heart. Using a gene\u2010editing platform, human induced pluripotent stem cell (hiPSCs) were engineered with a drug\u2010inducible expression cassette driving the adult cardiac troponin I (cTnI) regulatory isoform, a transition shown to be a rate\u2010limiting step in advancing sarcomeric maturation of hiPSC cardiac muscle (hiPSC\u2010CM) toward the adult state. Findings show that induction of the adult cTnI isoform resulted in the physiological acquisition of adult\u2010like cardiac contractile function in hiPSC\u2010CMs in\u2009vitro. Specifically, cTnI induction accelerated relaxation kinetics at baseline conditions, a result independent of alterations in the kinetics of the intracellular Ca<sup>2+<\/sup> transient. In comparison, isogenic unedited hiPSC\u2010CMs had no cTnI induction and no change in relaxation function. Temporal control of adult cTnI isoform induction did not alter other developmentally regulated sarcomere transitions, including myosin heavy chain isoform expression, nor did it affect expression of SERCA2a or phospholamban. Taken together, precision genetic targeting of sarcomere maturation via inducible TnI isoform switching enables physiologically relevant adult myocardium\u2010like contractile adaptations that are essential for beat\u2010to\u2010beat modulation of adult human heart performance. These findings have relevance to hiPSC\u2010CM structure\u2010function and drug\u2010discovery studies in\u2009vitro, as well as for potential future clinical applications of physiologically optimized hiPSC\u2010CM in cardiac regeneration\/repair.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[34],"resource_type":[75],"application_areas":[77],"therapeutic_areas":[54],"target_categories":[],"target_families":[],"targets":[],"resource_keyword":[],"class_list":["post-6374","resource_library","type-resource_library","status-publish","hentry","products_tags-cardioexcyte-96","resource_type-publication","application_areas-cell-ipscs-profiling","therapeutic_areas-cardiac-safety-cipa"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library\/6374","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library"}],"about":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/types\/resource_library"}],"wp:attachment":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/media?parent=6374"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/products_tags?post=6374"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_type?post=6374"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/application_areas?post=6374"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/therapeutic_areas?post=6374"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_categories?post=6374"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_families?post=6374"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/targets?post=6374"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_keyword?post=6374"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}