title: Distinct angiogenesis roles and surface markers of early and late endothelial progenitor cells revealed by functional group analyses.
abstract: BACKGROUND
  Endothelial progenitor cells (EPCs) play a fundamental role in post-natal vascular repair. Currently EPCs are defined as either early and late EPCs based on their biological properties and their time of appearance during in vitro culture. EPCs are rare and therefore optimizing isolation and culture is required before they can be applied as part of clinical therapies.
  
  
  RESULTS
  We compared the gene profiles of early/late EPCs to their ancestors CD133+ or CD34+ stem cells and to matured endothelial cells pinpointing novel biomarkers and stemness genes. Late EPCs were enriched with proliferation and angiogenesis genes, participating in endothelial tubulogenesis and hence neovascularization. Early EPCs expressed abundant inflammatory cytokines and paracrine angiogenic factors, thereby promoting angiogenesis in a paracrine manner. Transcription factors involved in EPC stemness were pinpointed in early EPCs (MAF/MAFB) and in late EPCs (GATA6/IRF6).
  
  
  CONCLUSIONS
  The detailed mRNA expression profiles and functional module analysis for different EPCs will help the development of novel therapeutic modalities targeting cardiovascular disease, tumor angiogenesis and various ischemia-related diseases.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Cheng-Chung
authors.initials: CC
authors.lastname: Cheng
authors.forename: Shing-Jyh
authors.initials: SJ
authors.lastname: Chang
authors.forename: Yu-Neng
authors.initials: YN
authors.lastname: Chueh
authors.forename: Tse-Shun
authors.initials: TS
authors.lastname: Huang
authors.forename: Po-Hsun
authors.initials: PH
authors.lastname: Huang
authors.forename: Shu-Meng
authors.initials: SM
authors.lastname: Cheng
authors.forename: Tsung-Neng
authors.initials: TN
authors.lastname: Tsai
authors.forename: Jaw-Wen
authors.initials: JW
authors.lastname: Chen
authors.forename: Hsei-Wei
authors.initials: HW
authors.lastname: Wang
mesh_terms: D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D042783:Endothelial Cells / Q000502:physiology*; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D006801:Humans; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D013234:Stem Cells / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism; D059467:Transcriptome
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D014157:Transcription Factors