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Characterization of Thymic Settling Progenitors in the Mouse Embryo Using In Vivo and In Vitro Assays
08:56

Characterization of Thymic Settling Progenitors in the Mouse Embryo Using In Vivo and In Vitro Assays

Published on: June 9, 2015

Biological and molecular evidence for existence of lymphoid-primed multipotent progenitors

Sidinh Luc1, Natalija Buza-Vidas, Sten Eirik W Jacobsen

  • 1Haematopoietic Stem Cell Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Headington, Oxford, OX3 9DS, UK.

Annals of the New York Academy of Sciences
|April 20, 2007
PubMed

Insights

Multipotent progenitors (MPPs) in adult bone marrow show distinct gene expression patterns, suggesting early lymphoid priming. These findings clarify hematopoietic stem cell (HSC) commitment pathways during development.

Area of Science:

  • Hematopoiesis and Stem Cell Biology
  • Molecular and Cellular Biology
  • Immunology

Background:

  • Recent studies suggest multipotent progenitors (MPPs) in adult bone marrow possess granulocyte-macrophage, B cell, and T cell potential, but limited megakaryocyte-erythroid (MkE) potential.
  • The existence of lymphoid-primed MPPs (LMPPs) challenges the concept of strict early separation into myeloid and lymphoid pathways for hematopoietic stem cells (HSCs).
  • The precise lineage commitment steps of HSCs, particularly the role and definition of LMPPs, remain under investigation, with some studies questioning their existence due to observed MkE potential in some LSKCD34(+)FLT3(hi) cells.

Purpose of the Study:

  • To compare the molecular signature of adult LMPPs with populations of LSK cells possessing pluripotent HSC activity.
  • To investigate the transcriptional differences between LMPPs and HSCs, focusing on lineage priming.
  • To explore whether the definition of LMPPs is conserved between fetal and adult hematopoiesis.

Main Methods:

  • Global gene expression analysis of adult LMPPs and HSC-enriched LSK cell populations.
  • Single-cell gene expression profiling to assess molecular signatures at the individual cell level.
  • Comparative analysis of transcriptional profiles to identify differentially expressed genes related to lineage commitment.

Main Results:

  • LMPPs exhibit downregulated transcriptional priming for MkE lineage genes compared to pluripotent HSCs.
  • LMPPs show upregulated expression of early lymphoid genes relative to pluripotent HSCs.
  • Evidence suggests that the LMPP phenotype is established during fetal development, indicating conserved early hematopoiesis.

Conclusions:

  • Adult LMPPs are transcriptionally distinct from pluripotent HSCs, characterized by reduced MkE and increased lymphoid gene priming.
  • These findings support alternative lineage commitment pathways beyond a strict myeloid/lymphoid bifurcation early in HSC differentiation.
  • The LMPP stage appears to be a conserved feature of hematopoiesis, present in both fetal and adult bone marrow.

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