On becoming a T cell, a convergence of factors kick it up a Notch along the way

Thompson, Patrycja K.; Zúñiga‐Pflücker, Juan Carlos

doi:10.1016/j.smim.2011.08.007

Cited by 56 publications

(37 citation statements)

References 160 publications

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“…Notch comes close to encompassing and enforcing all of these outcomes; however, other transcriptional regulators are required for Notch to instruct T-lineage adoption (21).…”

Section: An Overview Of the Intrathymic Intricacies Of T Cell Developmentioning

confidence: 99%

An Overview of the Intrathymic Intricacies of T Cell Development

Shah

Zúñiga‐Pflücker

2014

The Journal of Immunology

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198

157

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The generation of a functional and diverse repertoire of T cells occurs in the thymus from precursors arriving from the bone marrow. In this article, we introduce the various stages of mouse thymocyte development and highlight recent work using various in vivo, and, where appropriate, in vitro models of T cell development that led to discoveries in the regulation afforded by transcription factors and receptor–ligand signaling pathways in specifying, maintaining, and promoting the T cell lineage and the production of T cells. This review also discusses the role of the thymic microenvironment in providing a niche for the successful development of T cells. In particular, we focus on advances in Notch signaling and developments in Notch ligand interactions in this process.

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“…Notch comes close to encompassing and enforcing all of these outcomes; however, other transcriptional regulators are required for Notch to instruct T-lineage adoption (21).…”

Section: An Overview Of the Intrathymic Intricacies Of T Cell Developmentioning

confidence: 99%

An Overview of the Intrathymic Intricacies of T Cell Development

Shah

Zúñiga‐Pflücker

2014

The Journal of Immunology

Self Cite

198

157

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“…T cells originate from hematopoietic stem and precursor cells in the bone marrow or fetal liver, which migrate to the thymus and acquire T cell identity. Relatively small numbers of T cell progenitors migrate into the thymus per day, but they respond to the new environment by undergoing multiple rounds of proliferation, while initiating the T cell differentiation program (Rothenberg 2000; Petrie and Zuniga-Pflucker 2007; Rothenberg et al 2008; Love and Bhandoola 2011; Naito et al 2011; Thompson and Zúñiga-Pflücker 2011; Rothenberg 2014; Yui and Rothenberg 2014). They then undergo T cell lineage commitment, begin T cell receptor ( TCR ) rearrangements, and thus generate αβTCR or γδTCR-expressing T cells.…”

Section: Introductionmentioning

confidence: 99%

Cytokines, Transcription Factors, and the Initiation of T-Cell Development

Hosokawa

Rothenberg

2017

Cold Spring Harb Perspect Biol

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Multipotent blood progenitor cells migrate into the thymus and initiate the T cell differentiation program. T cell progenitor cells gradually acquire T cell characteristics while shedding their multipotentiality for alternative fates. This process is supported by extracellular signaling molecules, including Notch ligands and cytokines, provided by the thymic microenvironment. T cell development is associated with dynamic change of gene regulatory networks of transcription factors, which interact with these environmental signals. Together with Notch or pre-TCR signaling, cytokines always control proliferation, survival and differentiation of early T cells, but little is known regarding their crosstalk with transcription factors. However, recent results suggest ways that cytokines expressed in distinct intrathymic niches can specifically modulate key transcription factors. This review discusses how stage-specific roles of cytokines and transcription factors can jointly guide development of early T cells.

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“…Notch-pathway signalling induced by cell contact with the thymic microenvironment is known to be needed for this developmental progression, but substantial numbers of cells making this response do not appear for days, suggesting an indirect pathway or a developmental limitation on responsiveness [9,10]. Indeed, Notch signals appear to trigger different gene expression responses at different DN stages, and this provides opportunities for developmental fine-tuning by signals other than Notch.…”

Section: Introductionmentioning

confidence: 99%

Computational modelling of T-cell formation kinetics: output regulated by initial proliferation-linked deferral of developmental competence

Manesso

Chickarmane

Kueh

et al. 2013

J. R. Soc. Interface.

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Bone-marrow-derived progenitors must continually enter the thymus of an adult mouse to sustain T-cell homeostasis, yet only a few input cells per day are sufficient to support a yield of 5 Â 10 7 immature T-cells per dayand an eventual output of 1-2 Â 10 6 mature cells per day. While substantial progress has been made to delineate the developmental pathway of T-cell lineage commitment, still little is known about the relationship between differentiation competence and the remarkable expansion of the earliest (DN1 stage) T-cell progenitors. To address this question, we developed computational models where the probability to progress to the next stage (DN2) is related to division number. To satisfy differentiation kinetics and overall cell yield data, our models require that adult DN1 cells divide multiple times before becoming competent to progress into DN2 stage. Our findings were subsequently tested by in vitro experiments, where putative early and later-stage DN1 progenitors from the thymus were purified and their progression into DN2 was measured. These experiments showed that the two DN1 sub-populations divided with similar rates, but progressed to the DN2 stage with different rates, thus providing experimental evidence that DN1 cells increase their commitment probability in a cell-intrinsic manner as they undergo cell division. Proliferation-linked shifts in eligibility of DN1 cells to undergo specification thus control kinetics of T-cell generation.

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On becoming a T cell, a convergence of factors kick it up a Notch along the way

Cited by 56 publications

References 160 publications

An Overview of the Intrathymic Intricacies of T Cell Development

An Overview of the Intrathymic Intricacies of T Cell Development

Cytokines, Transcription Factors, and the Initiation of T-Cell Development

Computational modelling of T-cell formation kinetics: output regulated by initial proliferation-linked deferral of developmental competence

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