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Evidence for a novel route of adult hematopoietic stem-cell lineage commitment through Lin-Sca-1+Kit+Flt3hi (LSKFlt3hi) lymphoid-primed multipotent progenitors (LMPPs) with granulocyte/monocyte (GM) and lymphoid but little or no megakaryocyte/erythroid (MkE) potential was recently challenged, as LSKFlt3hi cells were reported to possess MkE potential. Herein, residual (1%-2%) MkE potential segregated almost entirely with LSKFlt3hi cells expressing the thrombopoietin receptor (Mpl), whereas LSKFlt3hiMpl- LMPPs lacked significant MkE potential in vitro and in vivo, but sustained combined GM and lymphoid potentials, and coexpressed GM and lymphoid but not MkE transcriptional lineage programs. Gradually increased transcriptional lymphoid priming in single LMPPs from Rag1GFP mice was shown to occur in the presence of maintained GM lineage priming, but gradually reduced GM lineage potential. These functional and molecular findings reinforce the existence of GM/lymphoid-restricted progenitors with dramatically down-regulated probability for committing toward MkE fates, and support that lineage restriction occurs through gradual rather than abrupt changes in specific lineage potentials.

Original publication

DOI

10.1182/blood-2007-08-108324

Type

Journal article

Journal

Blood

Publication Date

01/04/2008

Volume

111

Pages

3424 - 3434

Keywords

Animals, Antigens, Ly, Down-Regulation, Homeodomain Proteins, Lymphocytes, Membrane Proteins, Mice, Mice, Transgenic, Multipotent Stem Cells, Myeloid Cells, Proto-Oncogene Proteins c-kit, Receptors, Thrombopoietin, fms-Like Tyrosine Kinase 3