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

Research output: Contribution to journalArticle

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.

Details

Authors
  • Robert Månsson
  • Anne Hultquist
  • Sidinh Luc
  • Liping Yang
  • Kristina Anderson
  • Shabnam Kharazi
  • Suleiman Al-Hashmi
  • Karina Liuba
  • Lina Thorén
  • Jörgen Adolfsson
  • Natalija Buza-Vidas
  • Hong Qian
  • Shamit Soneji
  • Tariq Enver
  • Mikael Sigvardsson
  • Sten Eirik W Jacobsen
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Immunology in the medical area
Original languageEnglish
Pages (from-to)407-419
JournalImmunity
Volume26
Issue number4
Publication statusPublished - 2007
Publication categoryResearch
Peer-reviewedYes

Related research output

Luc, S., 2011, Lund Stem Cell Center. 257 p.

Research output: ThesisDoctoral Thesis (compilation)

Anderson, K., 2007, Hematopoietic Stem Cell Laboratory. 2001 p.

Research output: ThesisDoctoral Thesis (compilation)

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