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Molecular evidence for hierarchical transcriptional lineage priming in fetal and adult stem cells and multipotent progenitors.

Månsson, Robert LU ; Hultquist, Anne LU ; Luc, Sidinh LU ; Yang, Liping LU ; Anderson, Kristina LU ; Kharazi, Shabnam LU ; Al-Hashmi, Suleiman LU ; Liuba, Karina LU ; Thorén, Lina LU and Adolfsson, Jörgen LU , et al. (2007) In Immunity 26(4). p.407-419
Abstract
Recent studies implicated the existence of adult lymphoid-primed multipotent progenitors (LMPPs) with little or no megakaryocyte-erythroid potential, questioning common myeloid and lymphoid progenitors as obligate intermediates in hematopoietic stem cell (HSC) lineage commitment. However, the existence of LMPPs remains contentious. Herein, global and single-cell analyses revealed a hierarchical organization of transcriptional lineage programs, with downregulation of megakaryocyte-erythroid genes from HSCs to LMPPs, sustained granulocyte-monocyte priming, and upregulation of common lymphoid (but not B and T cell-specific) genes. These biological and molecular relationships, implicating almost mutual exclusion of megakaryocyte-erythroid and... (More)
Recent studies implicated the existence of adult lymphoid-primed multipotent progenitors (LMPPs) with little or no megakaryocyte-erythroid potential, questioning common myeloid and lymphoid progenitors as obligate intermediates in hematopoietic stem cell (HSC) lineage commitment. However, the existence of LMPPs remains contentious. Herein, global and single-cell analyses revealed a hierarchical organization of transcriptional lineage programs, with downregulation of megakaryocyte-erythroid genes from HSCs to LMPPs, sustained granulocyte-monocyte priming, and upregulation of common lymphoid (but not B and T cell-specific) genes. These biological and molecular relationships, implicating almost mutual exclusion of megakaryocyte-erythroid and lymphoid pathways, are established already in fetal hematopoiesis, as evidenced by existence of LMPPs in fetal liver. The identification of LMPPs and hierarchically ordered transcriptional activation and downregulation of distinct lineage programs is compatible with a model for HSC lineage commitment in which the probability for undergoing different lineage commitment fates changes gradually when progressing from HSCs to LMPPs. (Less)
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published
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Immunity
volume
26
issue
4
pages
407 - 419
publisher
Cell Press
external identifiers
  • wos:000246126400007
  • scopus:34247092922
ISSN
1074-7613
DOI
10.1016/j.immuni.2007.02.013
language
English
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yes
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ba2f5570-b526-4c93-a1d7-4ba48191670b (old id 167626)
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http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17433729&dopt=Abstract
date added to LUP
2007-07-23 15:34:48
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2017-11-19 03:36:30
@article{ba2f5570-b526-4c93-a1d7-4ba48191670b,
  abstract     = {Recent studies implicated the existence of adult lymphoid-primed multipotent progenitors (LMPPs) with little or no megakaryocyte-erythroid potential, questioning common myeloid and lymphoid progenitors as obligate intermediates in hematopoietic stem cell (HSC) lineage commitment. However, the existence of LMPPs remains contentious. Herein, global and single-cell analyses revealed a hierarchical organization of transcriptional lineage programs, with downregulation of megakaryocyte-erythroid genes from HSCs to LMPPs, sustained granulocyte-monocyte priming, and upregulation of common lymphoid (but not B and T cell-specific) genes. These biological and molecular relationships, implicating almost mutual exclusion of megakaryocyte-erythroid and lymphoid pathways, are established already in fetal hematopoiesis, as evidenced by existence of LMPPs in fetal liver. The identification of LMPPs and hierarchically ordered transcriptional activation and downregulation of distinct lineage programs is compatible with a model for HSC lineage commitment in which the probability for undergoing different lineage commitment fates changes gradually when progressing from HSCs to LMPPs.},
  author       = {Månsson, Robert and Hultquist, Anne and Luc, Sidinh and Yang, Liping and Anderson, Kristina and Kharazi, Shabnam and Al-Hashmi, Suleiman and Liuba, Karina and Thorén, Lina and Adolfsson, Jörgen and Buza-Vidas, Natalija and Qian, Hong and Soneji, Shamit and Enver, Tariq and Sigvardsson, Mikael and Jacobsen, Sten Eirik W},
  issn         = {1074-7613},
  language     = {eng},
  number       = {4},
  pages        = {407--419},
  publisher    = {Cell Press},
  series       = {Immunity},
  title        = {Molecular evidence for hierarchical transcriptional lineage priming in fetal and adult stem cells and multipotent progenitors.},
  url          = {http://dx.doi.org/10.1016/j.immuni.2007.02.013},
  volume       = {26},
  year         = {2007},
}