Location of Repository

A multipotent precursor in the thymus maps to the branching point of the T versus B lineage decision

By Claudia Benz and Conrad C. Bleul

Abstract

Hematopoietic precursors continuously colonize the thymus where they give rise mainly to T cells, but also to B and dendritic cells. The lineage relationship between these three cell types is unclear, and it remains to be determined if precursors in the thymus are multipotent, oligopotent, or lineage restricted. Resolution of this question necessitates the determination of the clonal differentiation potential of the most immature precursors in the thymus. Using a CC chemokine receptor 9–enhanced green fluorescent protein knock-in allele like a surface marker of unknown function, we identify a multipotent precursor present in bone marrow, blood, and thymus. Single cells of this precursor give rise to T, B, and dendritic cells. A more differentiated stage of this multipotent precursor in the thymus has lost the capacity to generate B but not T, dendritic, and myeloid cells. Thus, the newly identified precursor maps to the branching point of the T versus B lineage decision in the hematopoietic lineage hierarchy

Topics: Article
Publisher: The Rockefeller University Press
OAI identifier: oai:pubmedcentral.nih.gov:2212901
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles

    Preview

    Citations

    1. (2004). 31 ARTICLE thymocytes to the subcapsular microenvironment within the thymus is not an absolute requirement for T cell development.
    2. (2000). A clonogenic common myeloid progenitor that gives rise to all myeloid lineages.
    3. (1993). A developmental pathway involving four phenotypically and functionally distinct subsets of CD3 CD4 CD8 triple-negative adult mouse thymocytes defined by CD44 and CD25 expression.
    4. (1989). A murine early thymocyte developmental sequence is marked by transient expression of the interleukin 2 receptor.
    5. (2002). A role for CCR9 in T lymphocyte development and migration.
    6. (1985). A single stem cell can recolonize an embryonic thymus, producing phenotypically distinct T-cell populations.
    7. B lymphopoiesis in the thymus.
    8. (2003). Biology of hematopoietic stem cells and progenitors: implications for clinical application.
    9. (1991). CD4 expressed on earliest T-lineage precursor cells in the adult murine thymus.
    10. (2001). cell compartment is accompanied by loss of selfrenewal capacity.
    11. (2000). Chemokines define distinct microenvironments in the developing thymus.
    12. (2004). Circulating hematopoietic progenitors with T lineage potential.
    13. Cutting edge: identification of the orphan chemokine receptor GPR-9-6 as CCR9, the receptor for the chemokine TECK.
    14. (1999). Deficient T cell fate specification in mice with an induced inactivation of
    15. (1996). Dendritic cell development in culture from thymic precursor cells in the absence of granulocyte/macrophage colony-stimulating factor.
    16. (1991). Developmental potential of the earliest precursor cells from the adult mouse thymus.
    17. (1990). Differentiation of hematopoietic stem cells in irradiated mouse thymic lobes. Kinetics and phenotype of progeny.
    18. (2003). Efficient thymic immigration of B220( ) lymphoid-restricted bone marrow cells with T precursor potential.
    19. (1994). Generation of lymphohematopoietic cells from embryonic stem cells in culture.
    20. (2004). Heterogeneity among DN1 prothymocytes reveals multiple progenitors with different capacities to generate T cell and non-T cell lineages.
    21. (1997). Identification of clonogenic common lymphoid progenitors in mouse bone marrow.
    22. (1996). Identification of the earliest B lineage stage in mouse bone marrow.
    23. (2002). Induction of T cell development from hematopoietic progenitor cells by delta-like-1 in vitro.
    24. (2002). Lineage infidelity in myeloid cells with TCR gene rearrangement: a latent developmental potential of proT cells revealed by ectopic cytokine receptor signaling.
    25. lineage progenitors: new insights, but old questions remain.
    26. Lymphocyte development from hematopoietic stem cells.
    27. (2001). Mice lacking the CCR9 CC-chemokine receptor show a mild impairment of early T- and B-cell development and a reduction in T-cell receptor gammadelta( ) gut intraepithelial lymphocytes.
    28. (1995). Mouse thymus dendritic cells: kinetics of development and changes in surface markers during maturation.
    29. (2001). Notch 1-deficient common lymphoid precursors adopt a B cell fate in the thymus.
    30. (1994). Onset of TCR-beta gene rearrangement and role of TCRbeta expression during CD3 CD4 CD8 thymocyte differentiation.
    31. (1992). Phenotypic and functional characterization of c-kit expression during intrathymic T cell development.
    32. (1999). Precise developmental regulation of Ets family transcription factors during specification and commitment to the T cell lineage.
    33. (1986). Studies of thymocytopoiesis in rats and mice. I. Kinetics of appearance of thymocytes using a direct intrathymic adoptive transfer assay for thymocyte precursors.
    34. (1995). T-cell lineage commitment and cytokine responses of thymic progenitors.
    35. (1999). TECK, an efficacious chemoattractant for human thymocytes, uses GPR-9- 6/CCR9 as a specific receptor.
    36. The chemokine TECK is expressed by thymic and intestinal epithelial cells and attracts double- and single-positive thymocytes expressing the TECK receptor CCR9.
    37. (2005). The earliest subpopulation of mouse thymocytes contains potent T, significant macrophage and natural killer, but no B lymphocyte potential.
    38. (1993). Thymic dendritic cells and T cells develop simultaneously in the thymus from a common precursor population.
    39. (2003). Thymic medullary epithelial cell differentiation, thymocyte emigration, and the control of autoimmunity require lympho-epithelial cross talk via LTbetaR.
    40. (2003). Thymopoiesis independent of common lymphoid progenitors.
    41. (1992). Thymus-grafted SCID mice show transient thymopoiesis and limited depletion of V beta 11 T cells.
    42. (2002). Tracing lymphopoiesis with the aid of a pTalpha-controlled reporter gene.
    43. Transcription from the RAG1 locus marks the earliest lymphocyte progenitors in bone marrow.

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.