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  1. Article ; Online: The β-selection step shapes T-cell identity.

    Rothenberg, Ellen V

    Nature

    2023  Volume 613, Issue 7944, Page(s) 440–442

    MeSH term(s) T-Lymphocytes
    Language English
    Publishing date 2023-01-16
    Publishing country England
    Document type News ; Comment
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/d41586-023-00025-0
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  2. Article ; Online: Transcription factors specifically control change.

    Rothenberg, Ellen V

    Genes & development

    2023  Volume 36, Issue 21-24, Page(s) 1097–1099

    Abstract: Transcription factors are defined by their sequence-specific binding to DNA and by their selective impacts on gene expression, depending on specific binding sites. The factor binding motifs in the DNA should thus represent a blueprint of regulatory logic, ...

    Abstract Transcription factors are defined by their sequence-specific binding to DNA and by their selective impacts on gene expression, depending on specific binding sites. The factor binding motifs in the DNA should thus represent a blueprint of regulatory logic, suggesting that transcription factor binding patterns on the genome (e.g., measured by ChIP-seq) should indicate which target genes the factors are directly controlling. However, although genetic data confirm high impacts of transcription factor perturbation in embryology, transcription factors bind to far more sites than the number of genes they dynamically regulate, when measured by direct perturbation in a given cell type. Also, deletion of carefully chosen transcription factor binding sites often gives disappointingly weak results. In a new study in the previous issue of
    MeSH term(s) Transcription Factors/metabolism ; Embryonic Stem Cells/metabolism ; Gene Expression Regulation ; Binding Sites ; Octamer Transcription Factor-3/metabolism ; DNA/metabolism ; SOXB1 Transcription Factors/genetics ; Cell Differentiation/genetics
    Chemical Substances Transcription Factors ; Octamer Transcription Factor-3 ; DNA (9007-49-2) ; SOXB1 Transcription Factors
    Language English
    Publishing date 2023-01-06
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 806684-x
    ISSN 1549-5477 ; 0890-9369
    ISSN (online) 1549-5477
    ISSN 0890-9369
    DOI 10.1101/gad.350308.122
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  3. Article ; Online: The Heart of the Machine: Construction of T Cell Identity, Made Accessible.

    Rothenberg, Ellen V

    Journal of immunology (Baltimore, Md. : 1950)

    2022  Volume 209, Issue 7, Page(s) 1235–1236

    MeSH term(s) Heart ; T-Lymphocytes
    Language English
    Publishing date 2022-09-24
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.2200264
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  4. Book: Lineage determination in the immune system

    Rothenberg, Ellen V.

    (Immunological reviews ; 238)

    2010  

    Author's details Ellen V. Rothenberg, guest ed
    Series title Immunological reviews ; 238
    Collection
    Language English
    Size 262 S. : Ill., graph. Darst.
    Publisher Wiley-Blackwell
    Publishing place Oxford
    Publishing country Great Britain
    Document type Book
    HBZ-ID HT016599101
    Database Catalogue ZB MED Medicine, Health

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    Shelf markLoan statusLocation
    Se 160 -238- verfügbar in Königswinter Königswinter

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  5. Article ; Online: Logic and lineage impacts on functional transcription factor deployment for T-cell fate commitment.

    Rothenberg, Ellen V

    Biophysical journal

    2021  Volume 120, Issue 19, Page(s) 4162–4181

    Abstract: Transcription factors are the major agents that read the regulatory sequence information in the genome to initiate changes in expression of specific genes, both in development and in physiological activation responses. Their actions depend on site- ... ...

    Abstract Transcription factors are the major agents that read the regulatory sequence information in the genome to initiate changes in expression of specific genes, both in development and in physiological activation responses. Their actions depend on site-specific DNA binding and are largely guided by their individual DNA target sequence specificities. However, their action is far more conditional in a real developmental context than would be expected for simple reading of local genomic DNA sequence, which is common to all cells in the organism. They are constrained by slow-changing chromatin states and by interactions with other transcription factors, which affect their occupancy patterns of potential sites across the genome. These mechanisms lead to emergent discontinuities in function even for transcription factors with minimally changing expression. This is well revealed by diverse lineages of blood cells developing throughout life from hematopoietic stem cells, which use overlapping combinations of transcription factors to drive strongly divergent gene regulation programs. Here, using development of T lymphocytes from hematopoietic multipotent progenitor cells as a focus, recent evidence is reviewed on how binding specificity and dynamics, transcription factor cooperativity, and chromatin state changes impact the effective regulatory functions of key transcription factors including PU.1, Runx1, Notch-RBPJ, and Bcl11b.
    MeSH term(s) Cell Differentiation ; Cell Lineage ; Gene Expression Regulation ; Logic ; T-Lymphocytes
    Language English
    Publishing date 2021-04-08
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 218078-9
    ISSN 1542-0086 ; 0006-3495
    ISSN (online) 1542-0086
    ISSN 0006-3495
    DOI 10.1016/j.bpj.2021.04.002
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  6. Article ; Online: Single-cell insights into the hematopoietic generation of T-lymphocyte precursors in mouse and human.

    Rothenberg, Ellen V

    Experimental hematology

    2021  Volume 95, Page(s) 1–12

    Abstract: T-Cell development is a major branch of lymphoid development and a key output of hematopoiesis, especially in early life, but the molecular requirements for T-cell potential have remained obscure. Considerable advances have now been made toward solving ... ...

    Abstract T-Cell development is a major branch of lymphoid development and a key output of hematopoiesis, especially in early life, but the molecular requirements for T-cell potential have remained obscure. Considerable advances have now been made toward solving this problem through single-cell transcriptome studies, interfaced with in vitro differentiation assays that monitor potential efficiently at the single-cell level. This review focuses on a series of recent reports studying mouse and human early T-cell precursors, both in the developing fetus and in stringently purified postnatal samples of intrathymic and prethymic T-lineage precursors. Cross-comparison of results reveals a robustly conserved core program in mouse and human, but with some informative and provocative variations between species and between ontogenic states. Repeated findings are the multipotent progenitor regulatory signature of thymus-seeding cells and the proximity of the T-cell program to dendritic cell programs, especially to plasmacytoid dendritic cells in humans.
    MeSH term(s) Animals ; Antigens, Differentiation, T-Lymphocyte/analysis ; Cell Lineage ; Cell Movement ; Cell Separation ; Cells, Cultured ; Dendritic Cells/cytology ; Fetus/cytology ; Fetus/immunology ; Gene Expression Regulation, Developmental ; Hematopoiesis/genetics ; Humans ; Mice ; Multipotent Stem Cells/cytology ; Precursor Cells, T-Lymphoid/classification ; Precursor Cells, T-Lymphoid/cytology ; Receptors, Antigen, T-Cell, alpha-beta/genetics ; Repressor Proteins/physiology ; Single-Cell Analysis/methods ; Species Specificity ; Thymus Gland/cytology ; Thymus Gland/embryology ; Thymus Gland/growth & development ; Transcriptome ; Tumor Suppressor Proteins/physiology
    Chemical Substances Antigens, Differentiation, T-Lymphocyte ; BCL11B protein, human ; Bcl11b protein, mouse ; Receptors, Antigen, T-Cell, alpha-beta ; Repressor Proteins ; Tumor Suppressor Proteins
    Language English
    Publishing date 2021-01-14
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 185107-x
    ISSN 1873-2399 ; 0531-5573 ; 0301-472X
    ISSN (online) 1873-2399
    ISSN 0531-5573 ; 0301-472X
    DOI 10.1016/j.exphem.2020.12.005
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  7. Article ; Online: Multi-modular structure of the gene regulatory network for specification and commitment of murine T cells.

    Shin, Boyoung / Rothenberg, Ellen V

    Frontiers in immunology

    2023  Volume 14, Page(s) 1108368

    Abstract: T cells develop from multipotent progenitors by a gradual process dependent on intrathymic Notch signaling and coupled with extensive proliferation. The stages leading them to T-cell lineage commitment are well characterized by single-cell and bulk RNA ... ...

    Abstract T cells develop from multipotent progenitors by a gradual process dependent on intrathymic Notch signaling and coupled with extensive proliferation. The stages leading them to T-cell lineage commitment are well characterized by single-cell and bulk RNA analyses of sorted populations and by direct measurements of precursor-product relationships. This process depends not only on Notch signaling but also on multiple transcription factors, some associated with stemness and multipotency, some with alternative lineages, and others associated with T-cell fate. These factors interact in opposing or semi-independent T cell gene regulatory network (GRN) subcircuits that are increasingly well defined. A newly comprehensive picture of this network has emerged. Importantly, because key factors in the GRN can bind to markedly different genomic sites at one stage than they do at other stages, the genes they significantly regulate are also stage-specific. Global transcriptome analyses of perturbations have revealed an underlying modular structure to the T-cell commitment GRN, separating decisions to lose "stem-ness" from decisions to block alternative fates. Finally, the updated network sheds light on the intimate relationship between the T-cell program, which depends on the thymus, and the innate lymphoid cell (ILC) program, which does not.
    MeSH term(s) Mice ; Animals ; T-Lymphocytes/metabolism ; Gene Regulatory Networks ; Immunity, Innate ; Cell Lineage/genetics ; Receptors, Notch/metabolism ; Lymphocytes/metabolism
    Chemical Substances Receptors, Notch
    Language English
    Publishing date 2023-01-31
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2023.1108368
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  8. Article ; Online: T-cell commitment inheritance-an agent-based multi-scale model.

    Andersson, Emil / Rothenberg, Ellen V / Peterson, Carsten / Olariu, Victor

    NPJ systems biology and applications

    2024  Volume 10, Issue 1, Page(s) 40

    Abstract: T-cell development provides an excellent model system for studying lineage commitment from a multipotent progenitor. The intrathymic development process has been thoroughly studied. The molecular circuitry controlling it has been dissected and the ... ...

    Abstract T-cell development provides an excellent model system for studying lineage commitment from a multipotent progenitor. The intrathymic development process has been thoroughly studied. The molecular circuitry controlling it has been dissected and the necessary steps like programmed shut off of progenitor genes and T-cell genes upregulation have been revealed. However, the exact timing between decision-making and commitment stage remains unexplored. To this end, we implemented an agent-based multi-scale model to investigate inheritance in early T-cell development. Treating each cell as an agent provides a powerful tool as it tracks each individual cell of a simulated T-cell colony, enabling the construction of lineage trees. Based on the lineage trees, we introduce the concept of the last common ancestors (LCA) of committed cells and analyse their relations, both at single-cell level and population level. In addition to simulating wild-type development, we also conduct knockdown analysis. Our simulations predicted that the commitment is a three-step process that occurs on average over several cell generations once a cell is first prepared by a transcriptional switch. This is followed by the loss of the Bcl11b-opposing function approximately two to three generations later. This is when our LCA analysis indicates that the decision to commit is taken even though in general another one to two generations elapse before the cell actually becomes committed by transitioning to the DN2b state. Our results showed that there is decision inheritance in the commitment mechanism.
    MeSH term(s) T-Lymphocytes/physiology ; Cell Lineage ; Cell Differentiation/genetics ; Transcription Factors/genetics
    Chemical Substances Transcription Factors
    Language English
    Publishing date 2024-04-17
    Publishing country England
    Document type Journal Article
    ISSN 2056-7189
    ISSN (online) 2056-7189
    DOI 10.1038/s41540-024-00368-y
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  9. Article ; Online: Causal Gene Regulatory Network Modeling and Genomics: Second-Generation Challenges.

    Rothenberg, Ellen V

    Journal of computational biology : a journal of computational molecular cell biology

    2019  Volume 26, Issue 7, Page(s) 703–718

    MeSH term(s) Animals ; Chromatin/metabolism ; Embryonic Development/genetics ; Gene Expression Regulation, Developmental ; Gene Regulatory Networks ; Genomics ; Models, Genetic
    Chemical Substances Chromatin
    Language English
    Publishing date 2019-05-07
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2030900-4
    ISSN 1557-8666 ; 1066-5277
    ISSN (online) 1557-8666
    ISSN 1066-5277
    DOI 10.1089/cmb.2019.0098
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  10. Article ; Online: Multiplex, Quantitative, High-Resolution Imaging of Protein:Protein Complexes via Hybridization Chain Reaction.

    Schulte, Samuel J / Shin, Boyoung / Rothenberg, Ellen V / Pierce, Niles A

    ACS chemical biology

    2024  Volume 19, Issue 2, Page(s) 280–288

    Abstract: Signal amplification based on the mechanism of hybridization chain reaction (HCR) facilitates spatial exploration of gene regulatory networks by enabling multiplex, quantitative, high-resolution imaging of RNA and protein targets. Here, we extend these ... ...

    Abstract Signal amplification based on the mechanism of hybridization chain reaction (HCR) facilitates spatial exploration of gene regulatory networks by enabling multiplex, quantitative, high-resolution imaging of RNA and protein targets. Here, we extend these capabilities to the imaging of protein:protein complexes, using proximity-dependent cooperative probes to conditionally generate a single amplified signal if and only if two target proteins are colocalized within the sample. HCR probes and amplifiers combine to provide automatic background suppression throughout the protocol, ensuring that even if reagents bind nonspecifically in the sample, they will not generate amplified background. We demonstrate protein:protein imaging with a high signal-to-background ratio in human cells, mouse proT cells, and highly autofluorescent formalin-fixed paraffin-embedded (FFPE) human breast tissue sections. Further, we demonstrate multiplex imaging of three different protein:protein complexes simultaneously and validate that HCR enables accurate and precise relative quantitation of protein:protein complexes with subcellular resolution in an anatomical context. Moreover, we establish a unified framework for simultaneous multiplex, quantitative, high-resolution imaging of RNA, protein, and protein:protein targets, with one-step, isothermal, enzyme-free HCR signal amplification performed for all target classes simultaneously.
    MeSH term(s) Humans ; Animals ; Mice ; Nucleic Acid Hybridization/methods ; RNA ; Diagnostic Imaging ; Nucleic Acid Amplification Techniques
    Chemical Substances RNA (63231-63-0)
    Language English
    Publishing date 2024-01-17
    Publishing country United States
    Document type Journal Article
    ISSN 1554-8937
    ISSN (online) 1554-8937
    DOI 10.1021/acschembio.3c00431
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