Downregulation of Mpl marks the transition to lymphoid-primed multipotent progenitors with gradual loss of granulocyte-monocyte potential.
Författare
Summary, in English
Evidence for a novel route of adult hematopoietic stem cell lineage commitment through Lin(-)Sca-1(+)Kit(+)Flt3(hi) (LSKFlt3(hi)) lymphoid-primed multipotent progenitors (LMPPs) with granulocyte/monocyte (GM) and lymphoid but little or no megakaryocyte/erythroid (MkE) potential was recently challenged, as LSKFlt3(hi) cells were reported to possess MkE potential. Herein residual (1-2%) MkE potential segregated almost entirely with LSKFlt3(hi) cells expressing the thrombopoietin receptor (Mpl), whereas LSKFlt3(hi)Mpl(-) LMPPs lacked significant MkE potential in vitro and in vivo, but sustained combined GM and lymphoid potentials, and co-expressed GM and lymphoid but not MkE transcriptional lineage programs. Gradually increased transcriptional lymphoid priming in single LMPPs from Rag1(GFP) 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 downregulated probability for committing towards MkE fates, and support that lineage restriction occurs through gradual rather than abrupt changes in specific lineage potentials.
Avdelning/ar
Publiceringsår
2008
Språk
Engelska
Sidor
3424-3434
Publikation/Tidskrift/Serie
Blood
Volym
111
Issue
7
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
American Society of Hematology
Ämne
- Hematology
Status
Published
ISBN/ISSN/Övrigt
- ISSN: 1528-0020