title: ATP-binding cassette G-subfamily transporter 2 regulates cell cycle progression and asymmetric division in mouse cardiac side population progenitor cells.
abstract: BACKGROUND
  After cardiac injury, cardiac progenitor cells are acutely reduced and are replenished in part by regulated self-renewal and proliferation, which occurs through symmetric and asymmetric cellular division. Understanding the molecular cues controlling progenitor cell self-renewal and lineage commitment is critical for harnessing these cells for therapeutic regeneration. We previously have found that the cell surface ATP-binding cassette G-subfamily transporter 2 (Abcg2) influences the proliferation of cardiac side population (CSP) progenitor cells, but through unclear mechanisms.
  
  
  OBJECTIVE
  To determine the role of Abcg2 on cell cycle progression and mode of division in mouse CSP cells.
  
  
  RESULTS
  Herein, using CSP cells isolated from wild-type and Abcg2 knockout mice, we found that Abcg2 regulates G1-S cell cycle transition by fluorescence ubiquitination cell cycle indicators, cell cycle-focused gene expression arrays, and confocal live-cell fluorescent microscopy. Moreover, we found that modulation of cell cycle results in transition from symmetric to asymmetric cellular division in CSP cells lacking Abcg2.
  
  
  CONCLUSIONS
  Abcg2 modulates CSP cell cycle progression and asymmetric cell division, establishing a mechanistic link between this surface transporter and cardiac progenitor cell function. Greater understanding of progenitor cell biology and, in particular, the regulation of resident progenitor cell homeostasis is vital for guiding the future development of cell-based therapies for cardiac regeneration.
authors.affiliation: Cardiac Muscle Research Laboratory, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 77 Ave Louis Pasteur, NRB 431, Boston, MA 02115, USA.
authors.forename: Konstantina-Ioanna
authors.initials: KI
authors.lastname: Sereti
authors.forename: Angelos
authors.initials: A
authors.lastname: Oikonomopoulos
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Unno
authors.forename: Xin
authors.initials: X
authors.lastname: Cao
authors.forename: Yiling
authors.initials: Y
authors.lastname: Qiu
authors.forename: Ronglih
authors.initials: R
authors.lastname: Liao
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D060049:Asymmetric Cell Division / Q000235:genetics; D059447:Cell Cycle Checkpoints / Q000235:genetics; D002478:Cells, Cultured; D005434:Flow Cytometry; D059585:G1 Phase Cell Cycle Checkpoints; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D007700:Kinetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D018715:Microscopy, Video; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D034622:RNA Interference; D058985:Side-Population Cells / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D059008:Time-Lapse Imaging; D014162:Transfection
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; C501412:Abcg2 protein, mouse