{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T17:57:26Z","timestamp":1792259846577,"version":"4.4.0"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"25","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2018,12,18]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>\n              The adult mammalian heart displays a cardiomyocyte turnover rate of \u22481%\/y throughout postnatal life and after injuries such as myocardial infarction (MI), but the question of which cell types drive this low level of new cardiomyocyte formation remains contentious. Cardiac-resident stem cells marked by stem cell antigen-1 (Sca-1, gene name\n              <jats:italic>Ly6a<\/jats:italic>\n              ) have been proposed as an important source of cardiomyocyte renewal. However, the in vivo contribution of endogenous Sca-1\n              <jats:sup>+<\/jats:sup>\n              cells to the heart at baseline or after MI has not been investigated.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>\n              Here we generated\n              <jats:italic>Ly6a<\/jats:italic>\n              gene\u2013targeted mice containing either a constitutive or an inducible Cre recombinase to perform genetic lineage tracing of Sca-1\n              <jats:sup>+<\/jats:sup>\n              cells in vivo.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              We observed that the contribution of endogenous Sca-1\n              <jats:sup>+<\/jats:sup>\n              cells to the cardiomyocyte population in the heart was &lt;0.005% throughout all of cardiac development, with aging, or after MI. In contrast, Sca-1\n              <jats:sup>+<\/jats:sup>\n              cells abundantly contributed to the cardiac vasculature in mice during physiological growth and in the post-MI heart during cardiac remodeling. Specifically, Sca-1 lineage-traced endothelial cells expanded postnatally in the mouse heart after birth and into adulthood. Moreover, pulse labeling of Sca-1\n              <jats:sup>+<\/jats:sup>\n              cells with an inducible\n              <jats:italic>Ly6a<\/jats:italic>\n              -MerCreMer allele also revealed a preferential expansion of Sca-1 lineage-traced endothelial cells after MI injury in the mouse.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>\n              Cardiac-resident Sca-1\n              <jats:sup>+<\/jats:sup>\n              cells are not significant contributors to cardiomyocyte renewal in vivo. However, cardiac Sca-1\n              <jats:sup>+<\/jats:sup>\n              cells represent a subset of vascular endothelial cells that expand postnatally with enhanced responsiveness to pathological stress in vivo.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.118.035210","type":"journal-article","created":{"date-parts":[[2018,7,10]],"date-time":"2018-07-10T09:25:59Z","timestamp":1531214759000},"page":"2931-2939","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":97,"title":["Genetic Lineage Tracing of Sca-1\n            <sup>+<\/sup>\n            Cells Reveals Endothelial but Not Myogenic Contribution to the Murine Heart"],"prefix":"10.1161","volume":"138","author":[{"given":"Ronald J.","family":"Vagnozzi","sequence":"first","affiliation":[{"name":"Department of Pediatrics (R.J.V., M.A.S., S.-C.J.L., J.D.M.), Cincinnati Children\u2019s Hospital Medical Center, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle A.","family":"Sargent","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (R.J.V., M.A.S., S.-C.J.L., J.D.M.), Cincinnati Children\u2019s Hospital Medical Center, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suh-Chin J.","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (R.J.V., M.A.S., S.-C.J.L., J.D.M.), Cincinnati Children\u2019s Hospital Medical Center, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan J.","family":"Palpant","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia (N.J.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles E.","family":"Murry","sequence":"additional","affiliation":[{"name":"Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle (C.E.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffery D.","family":"Molkentin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (R.J.V., M.A.S., S.-C.J.L., J.D.M.), Cincinnati Children\u2019s Hospital Medical Center, OH."},{"name":"Howard Hughes Medical Institute (J.D.M.), Cincinnati Children\u2019s Hospital Medical Center, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13167-011-0068-z"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2016.2225"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11682"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1164680"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.05.026"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.029343"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.309710"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.111.243154"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00687-1"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.07.039"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2008.08.032"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1302.015"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13309"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1517201112"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9701"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2015.143"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2132126100"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2005-0386"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7930"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2013.09.004"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M313717200"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.307778"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.115.306397"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2010.08.017"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature02069"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2003.50104"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.12.4634"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005020195"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.181.1.93"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2006-0644"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.186.5.705"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-06-1918"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200003023420904"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24682"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0113014"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40246-016-0074-2"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","unstructured":"Li Y He L Huang X Bhaloo SI Zhao H Zhang S Pu W Tian X Li Y Liu Q Yu W Zhang L Liu X Liu K Tang J Zhang H Cai D Ralf AH Xu Q Lui KO Zhou B. Genetic lineage tracing of non-myocyte population by dual recombinases [published online ahead of print April 26 2018]. Circulation. doi: 10.1161\/CIRCULATIONAHA.118.034250. http:\/\/circ.ahajournals.org\/content\/early\/2018\/04\/25\/CIRCULATIONAHA.118.034250.long.","DOI":"10.1161\/CIRCULATIONAHA.118.034250"}],"updated-by":[{"DOI":"10.1161\/cir.0000000000000622","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2018,10,8]],"date-time":"2018-10-08T00:00:00Z","timestamp":1538956800000}}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCULATIONAHA.118.035210","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T08:38:08Z","timestamp":1715589488000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCULATIONAHA.118.035210"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,18]]},"references-count":37,"journal-issue":{"issue":"25","published-print":{"date-parts":[[2018,12,18]]}},"alternative-id":["10.1161\/CIRCULATIONAHA.118.035210"],"URL":"https:\/\/doi.org\/10.1161\/circulationaha.118.035210","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,12,18]]},"assertion":[{"value":"2018-03-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-06-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-07-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}