title: Bmi1 (+) cardiac progenitor cells contribute to myocardial repair following acute injury.
abstract: BACKGROUND
  The inability of the adult mammalian heart to replace cells lost after severe cardiac injury compromises organ function. Although the heart is one of the least regenerative organs in the body, evidence accumulated in recent decades indicates a certain degree of renewal after injury. We have evaluated the role of cardiac Bmi1 (+) progenitor cells (Bmi1-CPC) following acute myocardial infarction (AMI).
  
  
  METHODS
  Bmi1 (Cre/+);Rosa26 (YFP/+) (Bmi1-YFP) mice were used for lineage tracing strategy. After tamoxifen (TM) induction, yellow fluorescent protein (YFP) is expressed under the control of Rosa26 regulatory sequences in Bmi1 (+) cells. YFP(+) cells were tracked following myocardial infarction. Additionally, whole transcriptome analysis of isolated YFP(+) cells was performed in unchallenged hearts and after myocardial infarction.
  
  
  RESULTS
  Deep-sequencing analysis of Bmi1-CPC from unchallenged hearts suggests that this population expresses high levels of pluripotency markers. Conversely, transcriptome evaluation of Bmi1-CPC following AMI shows a rich representation of genes related to cell proliferation, movement, and cell cycle. Lineage-tracing studies after cardiac infarction show that the progeny of Bmi1-expressing cells contribute to de novo cardiomyocytes (CM) (13.8 ± 5 % new YFP(+) CM compared to 4.7 ± 0.9 % in age-paired non-infarcted hearts). However, apical resection of TM-induced day 1 Bmi1-YFP pups indicated a very minor contribution of Bmi1-derived cells to de novo CM.
  
  
  CONCLUSIONS
  Cardiac Bmi1 progenitor cells respond to cardiac injury, contributing to the generation of de novo CM in the adult mouse heart.
authors.affiliation: Cardiovascular Development and Repair Department, Spanish National Cardiovascular Research Center (CNIC), Madrid, Spain.|Current address: The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: Iñigo
authors.initials: I
authors.lastname: Valiente-Alandi
authors.affiliation: Cardiovascular Development and Repair Department, Spanish National Cardiovascular Research Center (CNIC), Madrid, Spain.|Current address: Vivebiotech, San Sebastian, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Albo-Castellanos
authors.affiliation: Cardiovascular Development and Repair Department, Spanish National Cardiovascular Research Center (CNIC), Madrid, Spain.|Immunology and Oncology Department, Spanish National Center for Biotechnology (CNB-CSIC), Madrid, Spain.
authors.forename: Diego
authors.initials: D
authors.lastname: Herrero
authors.affiliation: Unidad de Medicina Comparada, Cardiovascular Development and Repair Department, Spanish National Cardiovascular Research Center (CNIC), Madrid, Spain.
authors.forename: Iria
authors.initials: I
authors.lastname: Sanchez
authors.affiliation: Cardiovascular Development and Repair Department, Spanish National Cardiovascular Research Center (CNIC), Madrid, Spain. abernad@cnb.csic.es.|Immunology and Oncology Department, Spanish National Center for Biotechnology (CNB-CSIC), Madrid, Spain. abernad@cnb.csic.es.
authors.forename: Antonio
authors.initials: A
authors.lastname: Bernad
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D058948:Cell Tracking; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D063150:Polycomb Repressive Complex 1 / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects / Q000235:genetics*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology; D059467:Transcriptome
chemical_list: D001426:Bacterial Proteins; C489421:Bmi1 protein, mouse; C110853:Gt(ROSA)26Sor non-coding RNA, mouse; D008164:Luminescent Proteins; D011518:Proto-Oncogene Proteins; D022661:RNA, Untranslated; C054562:yellow fluorescent protein, Bacteria; D013629:Tamoxifen; D063150:Polycomb Repressive Complex 1
keywords: Bmi1; Cardiac progenitor cells; Myocardial infarction; Stem cells