Deciphering developmental stages of adult myelopoiesis.
The ability to subfractionate minor cellular subsets by multiparameter flow cytometry and to evaluate such cells for functional properties has been used to ascertain lineal relationships and detail developmental hierarchies in the hematopoietic system for more than 20 years. However, steady advances in technology combined with the use of novel cell surface markers continues to redefine the developmental landscape as novel subpopulations are purified and characterized. We recently used such an approach to stage progenitor cell hierarchy involved in myeloid development with the use of two markers, Slamf1 and Endoglin that have recently been shown to be associated with hematopoietic stem cells. Here, we provide additional characterization of these cellular subsets to further refine their developmental potential. Little or no alterations in lineage potential were observed in these subsets when evaluated in a BCL2 transgenic setting or in response to various growth factor combinations, although BCL2 significantly enhanced their in vitro readout. Gene expression patterns of functionally opposing transcription factors that are known to play key roles for the appropriate development into separate myeloid lineages were associated with the functional activity of prospectively isolated subsets. Multiple genes traditionally associated with early lymphopoiesis were observed in early candidate granulocyte/monocyte, but not early megakaryocytic and/or erythroid progenitor cells. When functionally evaluated, such early granulocyte/monocyte precursors displayed a latent lymphoid activity, which was pronounced in subsets bearing high expression of the tyrosine kinase receptor FLT3.
Pronk
Cornelis J
CJ
Institution for Experimental Medical Science, Immunology Section, Lund University, Lund, Sweden
Attema
Joanne
J
Rossi
Derrick J
DJ
Sigvardsson
Mikael
M
Bryder
David
D
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D019070:Cell Lineage / Q000502:physiology*; D000071063:Endoglin; D005434:Flow Cytometry / Q000379:methods; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D038042:Myelopoiesis / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D011956:Receptors, Cell Surface / Q000378:metabolism*; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D014157:Transcription Factors / Q000378:metabolism; D051941:fms-Like Tyrosine Kinase 3 / Q000378:metabolism
D015703:Antigens, CD; D000071063:Endoglin; C502004:Eng protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011956:Receptors, Cell Surface; C000604062:Slamf1 protein, mouse; D014157:Transcription Factors; C052617:Bcl2 protein, mouse; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; C497971:Flt3 protein, mouse; D051941:fms-Like Tyrosine Kinase 3