title: Prospective isolation of human erythroid lineage-committed progenitors.
abstract: Determining the developmental pathway leading to erythrocytes and being able to isolate their progenitors are crucial to understanding and treating disorders of red cell imbalance such as anemia, myelodysplastic syndrome, and polycythemia vera. Here we show that the human erythrocyte progenitor (hEP) can be prospectively isolated from adult bone marrow. We found three subfractions that possessed different expression patterns of CD105 and CD71 within the previously defined human megakaryocyte/erythrocyte progenitor (hMEP; Lineage(-) CD34(+) CD38(+) IL-3Rα(-) CD45RA(-)) population. Both CD71(-) CD105(-) and CD71(+) CD105(-) MEPs, at least in vitro, still retained bipotency for the megakaryocyte (MegK) and erythrocyte (E) lineages, although the latter subpopulation is skewed in differentiation toward the erythroid lineage. Notably, the proliferative and differentiation output of the CD71(intermediate(int)/+) CD105(+) subset of cells within the MEP population was completely restricted to the erythroid lineage with the loss of MegK potential. CD71(+) CD105(-) MEPs are erythrocyte-biased MEPs (E-MEPs) and CD71(int/+) CD105(+) cells are EPs. These previously unclassified populations may facilitate further understanding of the molecular mechanisms governing human erythroid development and serve as potential therapeutic targets in disorders of the erythroid lineage.
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305; Ludwig Center for Cancer Stem Cell Biology and Medicine at Stanford University, Stanford, CA 94305.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Mori
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305; Ludwig Center for Cancer Stem Cell Biology and Medicine at Stanford University, Stanford, CA 94305.
authors.forename: James Y
authors.initials: JY
authors.lastname: Chen
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305; Ludwig Center for Cancer Stem Cell Biology and Medicine at Stanford University, Stanford, CA 94305.
authors.forename: John V
authors.initials: JV
authors.lastname: Pluvinage
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305; Ludwig Center for Cancer Stem Cell Biology and Medicine at Stanford University, Stanford, CA 94305 jseita@stanford.edu irv@stanford.edu.
authors.forename: Jun
authors.initials: J
authors.lastname: Seita
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305; Ludwig Center for Cancer Stem Cell Biology and Medicine at Stanford University, Stanford, CA 94305 jseita@stanford.edu irv@stanford.edu.
authors.forename: Irving L
authors.initials: IL
authors.lastname: Weissman
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002458:Cell Fractionation; D019070:Cell Lineage / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation / Q000379:methods*; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects; D015672:Erythroid Precursor Cells / Q000166:cytology* / Q000187:drug effects; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016130:Immunophenotyping; D008533:Megakaryocytes / Q000166:cytology / Q000187:drug effects; D008954:Models, Biological; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; D016212:Transforming Growth Factor beta
keywords: endoglin; erythroid progenitor; hematopoiesis; lineage commitment; transcription factor