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Downregulation of Mpl marks the transition to lymphoid-primed multipotent progenitors with gradual loss of granulocyte-monocyte potential.

Luc, Sidinh LU ; Anderson, Kristina LU ; Kharazi, Shabnam LU ; Buza-Vidas, Natalija LU ; Böiers, Charlotta LU ; Jensen, Christina LU ; Ma, Zhi LU ; Wittmann, Lilian LU and Jacobsen, Sten Eirik W LU (2008) In Blood 111(7). p.3424-3434
Abstract
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
111
issue
7
pages
3424 - 3434
publisher
American Society of Hematology
external identifiers
  • pmid:18218856
  • wos:000254569300027
  • scopus:43549088844
ISSN
1528-0020
DOI
10.1182/blood-2007-08-108324
language
English
LU publication?
yes
id
5a11791d-5a04-4296-b06b-96bf1de4676d (old id 1021124)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18218856?dopt=Abstract
date added to LUP
2008-02-12 13:32:31
date last changed
2017-06-11 03:48:10
@article{5a11791d-5a04-4296-b06b-96bf1de4676d,
  abstract     = {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.},
  author       = {Luc, Sidinh and Anderson, Kristina and Kharazi, Shabnam and Buza-Vidas, Natalija and Böiers, Charlotta and Jensen, Christina and Ma, Zhi and Wittmann, Lilian and Jacobsen, Sten Eirik W},
  issn         = {1528-0020},
  language     = {eng},
  number       = {7},
  pages        = {3424--3434},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Downregulation of Mpl marks the transition to lymphoid-primed multipotent progenitors with gradual loss of granulocyte-monocyte potential.},
  url          = {http://dx.doi.org/10.1182/blood-2007-08-108324},
  volume       = {111},
  year         = {2008},
}