Myeloid or lymphoid promiscuity as a critical step in hematopoietic lineage commitment.
We demonstrate here that "promiscuous" expression of myeloid or lymphoid genes precedes lineage commitment in hematopoiesis. Prospectively purified single common myeloid progenitors (CMPs) coexpress myelo-erythroid but not lymphoid genes, whereas single common lymphoid progenitors (CLPs) coexpress T and B lymphoid but not myeloid genes. Genes unrelated to the adopted lineage are downregulated in bipotent and monopotent descendants of CMPs and CLPs. Promiscuous gene expression does not alter the biological potential of multipotent progenitors: CMPs with an activated endogenous M lysozyme locus yield normal proportions of myelo-erythroid colonies, and CLPs expressing the pre-T cell receptor alpha gene differentiate into normal numbers of B cells. Thus, the accessibility for multiple myeloid or lymphoid programs promiscuously may allow flexibility in fate commitments at these multipotent stages.
Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Palo Alto, CA 94305, USA.
Toshihiro
T
Miyamoto
Hiromi
H
Iwasaki
Boris
B
Reizis
Min
M
Ye
Thomas
T
Graf
Irving L
IL
Weissman
Koichi
K
Akashi
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D001853:Bone Marrow / Q000196:embryology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics*; D002478:Cells, Cultured; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D005838:Genotype; D006410:Hematopoiesis / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008533:Megakaryocytes / Q000166:cytology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D009113:Muramidase / Q000235:genetics / Q000378:metabolism; D022423:Myeloid Cells / Q000166:cytology / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D015533:Transcriptional Activation / Q000502:physiology
D008562:Membrane Glycoproteins; D011506:Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C090377:pre-T cell receptor alpha; D009113:Muramidase