title: Dynamic equilibrium of heterogeneous and interconvertible multipotent hematopoietic cell subsets.
abstract: Populations of hematopoietic stem cells and progenitors are quite heterogeneous and consist of multiple cell subsets with distinct phenotypic and functional characteristics. Some of these subsets also appear to be interconvertible and oscillate between functionally distinct states. The multipotent hematopoietic cell line EML has emerged as a unique model to study the heterogeneity and interconvertibility of multipotent hematopoietic cells. Here we describe extensive phenotypic and functional heterogeneity of EML cells which stems from the coexistence of multiple cell subsets. Each of these subsets is phenotypically and functionally heterogeneous, and displays distinct multilineage differentiation potential, cell cycle profile, proliferation kinetics, and expression pattern of HSC markers and some of the key lineage-associated transcription factors. Analysis of their maintenance revealed that on a population level all EML cell subsets exhibit cell-autonomous interconvertible properties, with the capacity to generate all other subsets and re-establish complete parental EML cell population. Moreover, all EML cell subsets generated during multiple cell generations maintain their distinct phenotypic and functional signatures and interconvertible properties. The model of EML cell line suggests that interconvertible multipotent hematopoietic cell subsets coexist in a homeostatically maintained dynamic equilibrium which is regulated by currently unknown cell-intrinsic mechanisms.
authors.affiliation: 1] Department of Cell Biology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA [2].
authors.forename: Wendy
authors.initials: W
authors.lastname: Weston
authors.affiliation: 1] Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA [2].
authors.forename: Jennifer
authors.initials: J
authors.lastname: Zayas
authors.affiliation: Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
authors.forename: Ruben
authors.initials: R
authors.lastname: Perez
authors.affiliation: Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
authors.forename: John
authors.initials: J
authors.lastname: George
authors.affiliation: 1] Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA [2] Department of Cell Biology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
authors.forename: Roland
authors.initials: R
authors.lastname: Jurecic
mesh_terms: D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism*; D015153:Blotting, Western; D002453:Cell Cycle; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger