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

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.

• Publication year

  2005

• Venue

  Journal of Experimental Medicine

• Publication date

  2005-07-04

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1084/jem.20050146PMID 15983065PMCID 2212901
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• The earliest subpopulation of mouse thymocytes contains potent T, significant macrophage, and natural killer cell but no B-lymphocyte potential.

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• Heterogeneity among DN1 prothymocytes reveals multiple progenitors with different capacities to generate T cell and non-T cell lineages.

  2004influential reference
• Circulating hematopoietic progenitors with T lineage potential

  2004influential reference
• Thymopoiesis independent of common lymphoid progenitors

  2003influential reference
• Thymic Medullary Epithelial Cell Differentiation, Thymocyte Emigration, and the Control of Autoimmunity Require Lympho–Epithelial Cross Talk via LTβR

  2003cited by this paper
• Efficient thymic immigration of B220+ lymphoid-restricted bone marrow cells with T precursor potential

  2003cited by this paper
• Early T Lineage Progenitors: New Insights, but Old Questions Remain

  2003cited by this paper
• Biology of hematopoietic stem cells and progenitors: implications for clinical application.

  2003cited by this paper
• Lineage infidelity in myeloid cells with TCR gene rearrangement: A latent developmental potential of proT cells revealed by ectopic cytokine receptor signaling

  2002cited by this paper
• A Role for CCR9 in T Lymphocyte Development and Migration1

  2002cited by this paper
• Tracing lymphopoiesis with the aid of a pTα-controlled reporter gene

  2002cited by this paper
• Tracing lymphopoiesis with the aid of a pTalpha-controlled reporter gene.

  2002cited by this paper
• Induction of T cell development from hematopoietic progenitor cells by delta-like-1 in vitro.

  2002cited by this paper
• Transcription from the RAG1 locus marks the earliest lymphocyte progenitors in bone marrow.

  2002cited by this paper
• Lymphocyte development from hematopoietic stem cells.

  2001cited by this paper
• 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 γδ+ gut intraepithelial lymphocytes

  2001cited by this paper
• 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.

  2001cited by this paper
• Upregulation of Flt3 expression within the bone marrow Lin(-)Sca1(+)c-kit(+) stem cell compartment is accompanied by loss of self-renewal capacity.

  2001cited by this paper
• Notch 1–Deficient Common Lymphoid Precursors Adopt a B Cell Fate in the Thymus

  2001cited by this paper
• B Lymphopoiesis in the Thymus1

  2000cited by this paper
• The chemokine TECK is expressed by thymic and intestinal epithelial cells and attracts double‐ and single‐positive thymocytes expressing the TECK receptor CCR9

  2000cited by this paper
• A clonogenic common myeloid progenitor that gives rise to all myeloid lineages

  2000cited by this paper
• B Lymphopoiesis in the Thymus

  2000cited by this paper
• Chemokines define distinct microenvironments in the developing thymus

  2000cited by this paper
• Cutting edge: identification of the orphan chemokine receptor GPR-9-6 as CCR9, the receptor for the chemokine TECK.

  1999cited by this paper
• Deficient T cell fate specification in mice with an induced inactivation of Notch1.

  1999cited by this paper
• TECK, an efficacious chemoattractant for human thymocytes, uses GPR-9-6/CCR9 as a specific receptor.

  1999cited by this paper
• Precise developmental regulation of Ets family transcription factors during specification and commitment to the T cell lineage.

  1999cited by this paper
• Identification of clonogenic common lymphoid progenitors in mouse bone marrow.

  1997cited by this paper
• Identification of the earliest B lineage stage in mouse bone marrow.

  1996cited by this paper
• Dendritic Cell Development in Culture from Thymic Precursor Cells in the Absence of Granulocyte/Macrophage Colony-stimulating Factor

  1996cited by this paper
• T-cell lineage commitment and cytokine responses of thymic progenitors.

  1995influential reference
• Mouse thymus dendritic cells: kinetics of development and changes in surface markers during maturation

  1995cited by this paper
• Generation of lymphohematopoietic cells from embryonic stem cells in culture.

  1994cited by this paper
• Onset of TCR-beta gene rearrangement and role of TCR-beta expression during CD3-CD4-CD8- thymocyte differentiation.

  1994cited by this paper
• 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.

  1993cited by this paper
• Thymic dendritic cells and T cells develop simultaneously in the thymus from a common precursor population

  1993cited by this paper
• Thymus-grafted SCID mice show transient thymopoiesis and limited depletion of V beta 11+ T cells

  1992cited by this paper
• Phenotypic and functional characterization of c-kit expression during intrathymic T cell development.

  1992cited by this paper
• CD4 expressed on earliest T-lineage precursor cells in the adult murine thymus

  1991cited by this paper
• Developmental potential of the earliest precursor cells from the adult mouse thymus

  1991influential reference
• Differentiation of hematopoietic stem cells in irradiated mouse thymic lobes. Kinetics and phenotype of progeny.

  1990cited by this paper
• A murine early thymocyte developmental sequence is marked by transient expression of the interleukin 2 receptor.

  1989cited by this paper
• Studies of thymocytopoiesis in rats and mice. I. Kinetics of appearance of thymocytes using a direct intrathymic adoptive transfer assay for thymocyte precursors

  1986cited by this paper
• A single stem cell can recolonize an embryonic thymus, producing phenotypically distinct T-cell populations

  1985cited by this paper

• Acute lymphoblastic leukaemia with T- and B-lineage defining markers.

  2025cites this paper
• The thymus road to a T cell: migration, selection, and atrophy

  2024cites this paper
• Speed and navigation control of thymocyte development by the fetal T‐cell gene regulatory network

  2023cites this paper
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  2021cites this paper
• The transcription factors GFI1 and GFI1B as modulators of the innate and acquired immune response.

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• Interleukin 7 receptor drives Early T lineage Progenitor expansion

  2021cites this paper
• Inside the biology of early T-cell precursor acute lymphoblastic leukemia: the perfect trick

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• Multipotent RAG1+ progenitors emerge directly from haemogenic endothelium in human pluripotent stem cell-derived haematopoietic organoids

  2020cites this paper
• ETP‐ALL with aberrant B marker expression: Case series and a brief review of literature

  2019cites this paper
• Stable lines and clones of long-term proliferating normal, genetically unmodified murine common lymphoid progenitors.

  2018cites this paper
• T cell acute lymphoblastic leukemia (T-ALL): New insights into the cellular origins and infiltration mechanisms common and unique among hematologic malignancies.

  2017cites this paper
• 10 The Role of PAX 5 in ALL

  2017cites this paper
• Development of Immune System Organs

  2017cites this paper
• A missense mutation in zbtb17 blocks the earliest steps of T cell differentiation in zebrafish

  2017cites this paper
• Introduction : T-cell identity and processing of T-cell progenitors

  2016cites this paper
• Forward Genetic Screens in Zebrafish Identify Pre-mRNA-Processing Pathways Regulating Early T Cell Development

  2016cites this paper
• Transcriptional Regulation of T Cell Lineage Commitment

  2016cites this paper
• An investigation of the role of TRIB2 in steady state and stressed haematopoiesis

  2016cites this paper
• Forging T-Lymphocyte Identity: Intersecting Networks of Transcriptional Control.

  2016cites this paper
• A stromal cell free culture system generates mouse pro‐T cells that can reconstitute T‐cell compartments in vivo

  2015cites this paper
• Role of MAPK and NF-κB signalling pathways in the regulation of the human GM-CSF gene in normal and leukaemic blood cells

  2015cites this paper
• Discrete roles of canonical and non-canonical Wnt signaling in hematopoiesis and lymphopoiesis

  2015cites this paper
• Transcriptional regulation of innate and adaptive lymphocyte lineages.

  2015cites this paper
• Versatility of stem and progenitor cells and the instructive actions of cytokines on hematopoiesis

  2015cites this paper
• Irf4 Regulates the Choice between T Lymphoid-Primed Progenitor and Myeloid Lineage Fates during Embryogenesis.

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• The development and function of thymic B cells

  2015cites this paper
• Les lymphocytes T régulateurs périphériques qui recirculent dans le thymus inhibent le développement de leurs précurseurs

  2014cites this paper
• Transcriptional control of early T and B cell developmental choices.

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• T-lineage specification and commitment requires constraint of myeloid gene expression programs by Hes1

  2014cites this paper
• Developmental gene networks: a triathlon on the course to T cell identity

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• Concise Review: Hematopoietic Stem Cell Transplantation: Targeting the Thymus

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• Global transcriptional analysis of primitive thymocytes reveals accelerated dynamics of T cell specification in fetal stages

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• Factors and networks that underpin early hematopoiesis.

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  2011cites this paper
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  2011cites this paper
• Mechanisms of T cell development and transformation.

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• Growth factor independence 1 (Gfi1) as a regulator of lymphocyte development and activation.

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  2010cites this paper
• Eliciting the T cell fate with Notch.

  2010influential citation
• Molecular and cellular basis of T cell lineage commitment.

  2010influential citation
• Developmental Biology of Mammalian T-Cell Progenitors: From Early Lymphoid Progenitors to Thymus-Colonizing Cells

  2010cites this paper
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• Multiple extrathymic precursors contribute to T-cell development with different kinetics.

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• CCR7/CCR9: knockin' on the thymus door.

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• CCR7 and CCR9 together recruit hematopoietic progenitors to the adult thymus.

  2010cites this paper
• T‐cell lineage determination

  2010influential citation
• CC chemokine receptor 7 and 9 double-deficient hematopoietic progenitors are severely impaired in seeding the adult thymus.

  2010cites this paper
• Regeneration of dendritic cells in aged mice

  2010cites this paper
• Functions of notch signaling in the immune system: consensus and controversies.

  2010cites this paper
• Early T cell development and the pitfalls of potential.

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• E proteins and the regulation of early lymphocyte development

  2010influential citation
• Awakening lineage potential by Ikaros-mediated transcriptional priming.

  2010cites this paper
• Shaping up a lineage--lessons from B lymphopoesis.

  2010cites this paper
• B‐cell development: one problem, multiple solutions

  2010cites this paper
• Intrathymic transplantation of bone marrow-derived progenitors provides long-term thymopoiesis.

  2010cites this paper
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• Feeding the fire: the role of defective bone marrow function in exacerbating thymic involution.

  2010cites this paper
• The intrathymic crossroads of T and NK cell differentiation

  2010cites this paper
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  2009cites this paper
• Development of T Lymphocytes

  2009cites this paper
• Molecular and biological aspects of primary immunodeficiency

  2009cites this paper
• Evolution of genetic networks underlying the emergence of thymopoiesis in vertebrates.

  2009cites this paper
• From the bone marrow to the thymus: the road map of early stages of T-cell development.

  2009cites this paper
• Models of haematopoiesis: seeing the wood for the trees

  2009cites this paper
• Genome-wide lineage-specific transcriptional networks underscore Ikaros-dependent lymphoid priming in hematopoietic stem cells.

  2009cites this paper
• A new paradigm for hematopoietic cell lineages: revision of the classical concept of the myeloid-lymphoid dichotomy.

  2009cites this paper
• Untangling the T branch of the hematopoiesis tree.

  2009cites this paper
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  2009cites this paper