Delineating the cellular pathways of hematopoietic lineage commitment.
The prevailing model for adult hematopoiesis postulates that the first lineage commitment step results in a strict separation of common myeloid and common lymphoid pathways. However, the recent identification of granulocyte/monocyte (GM)-lymphoid restricted lymphoid-primed multipotent progenitors (LMPPs) and primitive common myeloid progenitors (CMPs) within the "HSC" compartment provide compelling support for establishment of independent GM-megakaryocyte/erythroid (GM-MkE) and GM-lymphoid commitment pathways as decisive early lineage fate decisions. These changes in lineage potentials are corroborated by corresponding changes in multilineage transcriptional priming, as LMPPs down-regulate MkE priming but become GM-lymphoid transcriptionally primed, whereas CMPs are GM-MkE primed. These distinct biological and molecular relationships are established already in the fetal liver.
Luc
Sidinh
S
Haematopoietic Stem Cell Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.
Buza-Vidas
Natalija
N
Jacobsen
Sten Eirik W
SE