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Identification of Flt3(+) lympho-myeloid stem cells lacking erythro-megakaryocytic potential: A revised road map for adult blood lineage commitment

Adolfsson, Jörgen LU ; Månsson, Robert LU ; Buza-Vidas, Natalija LU ; Hultquist, Anne LU ; Liuba, Karina LU ; Jensen, Christina LU ; Bryder, David LU ; Yang, Liping LU ; Borge, OJ and Thorén, Lina LU , et al. (2005) In Cell 121(2). p.295-306
Abstract
All blood cell lineages derive from a common hematopoietic stem cell (HSC). The current model implicates that the first lineage commitment step of adult pluripotent HSCs results in a strict separation into common lymphoid and common myeloid precursors. We present evidence for a population of cells which, although sustaining a high proliferative and combined lympho-myeloid differentiation potential, have lost the ability to adopt erythroid and megakaryocyte lineage fates. Cells in the Lin-Sca-1+c-kit+ HSC compartment coexpressing high levels of the tyrosine kinase receptor Flt3 sustain granulocyte, monocyte, and B and T cell potentials but in contrast to Lin-Sca-1(+)ckit(+)Flt3(-) HSCs fail to produce significant erythroid and... (More)
All blood cell lineages derive from a common hematopoietic stem cell (HSC). The current model implicates that the first lineage commitment step of adult pluripotent HSCs results in a strict separation into common lymphoid and common myeloid precursors. We present evidence for a population of cells which, although sustaining a high proliferative and combined lympho-myeloid differentiation potential, have lost the ability to adopt erythroid and megakaryocyte lineage fates. Cells in the Lin-Sca-1+c-kit+ HSC compartment coexpressing high levels of the tyrosine kinase receptor Flt3 sustain granulocyte, monocyte, and B and T cell potentials but in contrast to Lin-Sca-1(+)ckit(+)Flt3(-) HSCs fail to produce significant erythroid and megakaryocytic progeny. This distinct lineage restriction site is accompanied by downregulation of genes for regulators of erythroid and megakaryocyte development. In agreement with representing a lymphoid primed progenitor, Lin(-)Sca-l(+)c-kit(+)CD34(+)Flt3(+) cells display upregulated IL-7 receptor gene expression. Based on these observations, we propose a revised road map for adult blood lineage development. (Less)
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publication status
published
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Cell
volume
121
issue
2
pages
295 - 306
publisher
Cell Press
external identifiers
  • pmid:15851035
  • wos:000228705000016
  • scopus:20244387299
ISSN
1097-4172
DOI
10.1016/j.cell.2005.02.013
language
English
LU publication?
yes
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de23da2c-25f7-44a2-bd88-72ad5ae6202c (old id 244523)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15851035
date added to LUP
2007-08-14 16:03:53
date last changed
2017-11-12 03:30:35
@article{de23da2c-25f7-44a2-bd88-72ad5ae6202c,
  abstract     = {All blood cell lineages derive from a common hematopoietic stem cell (HSC). The current model implicates that the first lineage commitment step of adult pluripotent HSCs results in a strict separation into common lymphoid and common myeloid precursors. We present evidence for a population of cells which, although sustaining a high proliferative and combined lympho-myeloid differentiation potential, have lost the ability to adopt erythroid and megakaryocyte lineage fates. Cells in the Lin-Sca-1+c-kit+ HSC compartment coexpressing high levels of the tyrosine kinase receptor Flt3 sustain granulocyte, monocyte, and B and T cell potentials but in contrast to Lin-Sca-1(+)ckit(+)Flt3(-) HSCs fail to produce significant erythroid and megakaryocytic progeny. This distinct lineage restriction site is accompanied by downregulation of genes for regulators of erythroid and megakaryocyte development. In agreement with representing a lymphoid primed progenitor, Lin(-)Sca-l(+)c-kit(+)CD34(+)Flt3(+) cells display upregulated IL-7 receptor gene expression. Based on these observations, we propose a revised road map for adult blood lineage development.},
  author       = {Adolfsson, Jörgen and Månsson, Robert and Buza-Vidas, Natalija and Hultquist, Anne and Liuba, Karina and Jensen, Christina and Bryder, David and Yang, Liping and Borge, OJ and Thorén, Lina and Anderson, Kristina and Sitnicka Quinn, Ewa and Sasaki, Yutaka and Sigvardsson, Mikael and Jacobsen, Sten Eirik W},
  issn         = {1097-4172},
  language     = {eng},
  number       = {2},
  pages        = {295--306},
  publisher    = {Cell Press},
  series       = {Cell},
  title        = {Identification of Flt3(+) lympho-myeloid stem cells lacking erythro-megakaryocytic potential: A revised road map for adult blood lineage commitment},
  url          = {http://dx.doi.org/10.1016/j.cell.2005.02.013},
  volume       = {121},
  year         = {2005},
}