Notch2 complements Notch1 to mediate inductive signaling that initiates early T cell development

Romero-Wolf, Maile; Shin, Boyoung; Zhou, Wen; Koizumi, Maria; Rothenberg, Ellen V.; Hosokawa, Hiroyuki

doi:10.1083/jcb.202005093

Cited by 33 publications

(64 citation statements)

References 55 publications

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“…[33] Another representative of constitutively expressed factors with context dependent roles for early T cell development is Notch family members. [34,62,63] Notch acts not only as a cell surface receptor, but also as a transcription factor. After Notch receptor recognizes Notch ligands, the intracellular domain of Notch (ICN) is proteolytically released and becomes a TF with the DNA binding protein, RBPJ.…”

Section: Cofactor Redeployment Modelmentioning

confidence: 99%

“…Specific loss of Runx proteins or cell surface Notch proteins was observed at 3 days post-sgRNA introduction (day 5 or 13 of overall culture for Phase 1 or Phase 2, respectively). [34,35] Thus, we succeeded in establishing the acute and stage-specific deletion system before and after T lineage commitment, which allows us to analyze effects of targeted genes disruption within 3 days.…”

Section: Stage-specific Deletion Of Target Genes In Phase 1 and Phasementioning

confidence: 99%

“…Importantly, we also found that Notch1, Notch2 and would delineate separation of pre-commitment T progenitors from alternative PU.1-dependent lineages (Figure 4B). [34,86] Therefore,…”

Section: Notch Family Membersmentioning

confidence: 99%

“…Runx1 and Notch are not the only TFs known to shift to different genomic sites between different developmental stages. [34,35] Bcl11b itself can act completely differently in two different types of lymphocytes, pro-T cells and type 2 ILCs (ILC2s). [10] There are strong global similarities between the early specification and commitment programs of T and ILC lineage cells, as shown by a recent single-cell analysis of ILC precursors distinguished by TCF1 expression.…”

Section: Bcl11b In Pro-t Cells Versus Ilc2 Cellsmentioning

confidence: 99%

“…[12] In this review, we focus on an unexpected new layer of regulatory network, mediated by stage-specific TFs, PU.1 and Bcl11b, with stage-specific actions of stably expressed and continuously required factors, Runx and Notch family members, in the T lineage commitment. [26,27,[33][34][35]…”

Section: Introductionmentioning

confidence: 99%

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Transcription factors regulate early T cell development via redeployment of other factors

2021

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Establishment of cell lineage identity from multipotent progenitors is controlled by cooperative actions of lineage-specific and stably expressed transcription factors, combined with input from environmental signals. Lineage-specific master transcription factors activate and repress gene expression by recruiting consistently expressed transcription factors and chromatin modifiers to their target loci. Recent technical advances in genome-wide and multi-omics analysis have shed light on unexpected mechanisms that underlie more complicated actions of transcription factors in cell fate decisions. In this review, we discuss functional dynamics of stably expressed and continuously required factors, Notch and Runx family members, throughout developmental stages of early T cell development in the thymus. Pre-and post-commitment stagespecific transcription factors induce dynamic redeployment of Notch and Runx binding genomic regions. Thus, together with stage-specific transcription factors, shared transcription factors across distinct developmental stages regulate acquisition of T lineage identity.

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Section: Cofactor Redeployment Modelmentioning

confidence: 99%

Section: Stage-specific Deletion Of Target Genes In Phase 1 and Phasementioning

confidence: 99%

“…Importantly, we also found that Notch1, Notch2 and would delineate separation of pre-commitment T progenitors from alternative PU.1-dependent lineages (Figure 4B). [34,86] Therefore,…”

Section: Notch Family Membersmentioning

confidence: 99%

Section: Bcl11b In Pro-t Cells Versus Ilc2 Cellsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Transcription factors regulate early T cell development via redeployment of other factors

2021

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Notch1 deficiency alters the migratory behavior of developing T cells and calcium signaling in the thymus of medaka

et al. 2021

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The differentiation of T cells from lymphoid progenitors in the thymus follows sequential developmental stages that constantly require interaction with thymic epithelial cells. Several distinct aspects of early T cell development depend on the activation of Notch receptors on thymocytes, while the selection of thymocytes at later stages are believed to be Notch independent. Using reverse genetic approaches and whole‐thymus live imaging in an in vivo teleost model, the medaka, we report that Notch1 signals is required for proliferation and specification of developing T cells as well as involved in their selection in the thymus. We reveal that Notch1 controls the migratory behavior of thymocytes through controlling the chemokine receptor Ccr9b and thereby influence the T cell receptor (TCR) activation. Hence, we propose that, in lower vertebrates, the function of Notch signaling extends to all stages of T cell development, except when thymocytes undergo TCRβ rearrangement.

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Notch signaling in adipose tissue macrophages prevents diet‐induced inflammation and metabolic dysregulation

Siouti,

Salagianni,

Manioudaki

et al. 2024

Eur J Immunol

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The importance of macrophages in adipose tissue (AT) homeostasis and inflammation is well established. However, the potential cues that regulate their function remain incompletely understood. To bridge this important gap, we sought to characterize novel pathways involved using a mouse model of diet‐induced obesity. By performing transcriptomics analysis of AT macrophages (ATMs), we found that late‐stage ATMs from high‐fat diet mice presented with perturbed Notch signaling accompanied by robust proinflammatory and metabolic changes. To explore the hypothesis that the deregulated Notch pathway contributes to the development of AT inflammation and diet‐induced obesity, we employed a genetic approach to abrogate myeloid Notch1 and Notch2 receptors. Our results revealed that the combined loss of Notch1 and Notch2 worsened obesity‐related metabolic dysregulation. Body and AT weight gain was higher, blood glucose levels increased and metabolic parameters were substantially worsened in deficient mice fed high‐fat diet. Moreover, serum insulin and leptin were elevated as were triglycerides. Molecular analysis of ATMs showed that deletion of Notch receptors escalated inflammation through the induction of an M1‐like pro‐inflammatory phenotype. Our findings thus support a protective role of myeloid Notch signaling in adipose tissue inflammation and metabolic dysregulation.

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Notch2 complements Notch1 to mediate inductive signaling that initiates early T cell development

Cited by 33 publications

References 55 publications

Transcription factors regulate early T cell development via redeployment of other factors

Transcription factors regulate early T cell development via redeployment of other factors

Notch1 deficiency alters the migratory behavior of developing T cells and calcium signaling in the thymus of medaka

Notch signaling in adipose tissue macrophages prevents diet‐induced inflammation and metabolic dysregulation

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