Elucidation of the phenotypic, functional, and molecular topography of a myeloerythroid progenitor cell hierarchy.
The major myeloid blood cell lineages are generated from hematopoietic stem cells by differentiation through a series of increasingly committed progenitor cells. Precise characterization of intermediate progenitors is important for understanding fundamental differentiation processes and a variety of disease states, including leukemia. Here, we evaluated the functional in vitro and in vivo potentials of a range of prospectively isolated myeloid precursors with differential expression of CD150, Endoglin, and CD41. Our studies revealed a hierarchy of myeloerythroid progenitors with distinct lineage potentials. The global gene expression signatures of these subsets were consistent with their functional capacities, and hierarchical clustering analysis suggested likely lineage relationships. These studies provide valuable tools for understanding myeloid lineage commitment, including isolation of an early erythroid-restricted precursor, and add to existing models of hematopoietic differentiation by suggesting that progenitors of the innate and adaptive immune system can separate late, following the divergence of megakaryocytic/erythroid potential.
Pronk
Cornelis J H
CJ
Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, BMC I13, 221 84 Lund, Sweden; Immunology Unit, Institution for Experimental Medical Science, Lund University, BMC I13, 221 84 Lund, Sweden.
Rossi
Derrick J
DJ
Månsson
Robert
R
Attema
Joanne L
JL
Norddahl
Gudmundur Logi
GL
Chan
Charles Kwok Fai
CK
Sigvardsson
Mikael
M
Weissman
Irving L
IL
Bryder
David
D
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D001792:Blood Platelets / Q000166:cytology; D002451:Cell Compartmentation; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002469:Cell Separation; D002999:Clone Cells; D000071063:Endoglin; D015672:Erythroid Precursor Cells / Q000166:cytology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016678:Genome; D006098:Granulocytes / Q000166:cytology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D023461:Myeloid Progenitor Cells / Q000166:cytology*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1
D015703:Antigens, CD; D000071063:Endoglin; C502004:Eng protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D011956:Receptors, Cell Surface; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1