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  1. AU="Marchi, Francisco"
  2. AU="Samyra R Cox"
  3. AU="Steffan‐Dewenter, Ingolf"
  4. AU="Mostafa Ahmed Khairy"
  5. AU=Wilkes M S
  6. AU="Zhong, Baichang"
  7. AU="Kirsch, Harald"
  8. AU=Gibson Spencer J

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  1. Artikel ; Online: E-cadherin is regulated by GATA-2 and marks the early commitment of mouse hematopoietic progenitors to the basophil and mast cell fates.

    Wanet, Anaïs / Bassal, Mahmoud A / Patel, Sweta B / Marchi, Francisco / Mariani, Samanta A / Ahmed, Nouraiz / Zhang, Haoran / Borchiellini, Marta / Chen, Sisi / Zhang, Junyan / Di Ruscio, Annalisa / Miyake, Kensuke / Tsai, Mindy / Paranjape, Anuya / Park, Shin-Young / Karasuyama, Hajime / Schroeder, Timm / Dzierzak, Elaine / Galli, Stephen J /
    Tenen, Daniel G / Welner, Robert S

    Science immunology

    2021  Band 6, Heft 56

    Abstract: E-cadherin is a calcium-dependent cell-cell adhesion molecule extensively studied for its involvement in tissue formation, epithelial cell behavior, and suppression of cancer. However, E-cadherin expression in the hematopoietic system has not been fully ... ...

    Abstract E-cadherin is a calcium-dependent cell-cell adhesion molecule extensively studied for its involvement in tissue formation, epithelial cell behavior, and suppression of cancer. However, E-cadherin expression in the hematopoietic system has not been fully elucidated. Combining single-cell RNA-sequencing analyses and immunophenotyping, we revealed that progenitors expressing high levels of E-cadherin and contained within the granulocyte-monocyte progenitors (GMPs) fraction have an enriched capacity to differentiate into basophils and mast cells. We detected E-cadherin expression on committed progenitors before the expression of other reported markers of these lineages. We named such progenitors pro-BMPs (pro-basophil and mast cell progenitors). Using RNA sequencing, we observed transcriptional priming of pro-BMPs to the basophil and mast cell lineages. We also showed that GATA-2 directly regulates E-cadherin expression in the basophil and mast cell lineages, thus providing a mechanistic connection between the expression of this cell surface marker and the basophil and mast cell fate specification.
    Mesh-Begriff(e) Animals ; Basophils/physiology ; Cadherins/genetics ; Cell Differentiation/genetics ; Cell Differentiation/immunology ; Cell Lineage/genetics ; Cell Lineage/immunology ; Cells, Cultured ; GATA2 Transcription Factor/metabolism ; Hematopoietic Stem Cells/physiology ; Mast Cells/physiology ; Mice ; Primary Cell Culture ; RNA-Seq ; Single-Cell Analysis
    Chemische Substanzen Cadherins ; Cdh1 protein, mouse ; GATA2 Transcription Factor ; Gata2 protein, mouse
    Sprache Englisch
    Erscheinungsdatum 2021-02-04
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2470-9468
    ISSN (online) 2470-9468
    DOI 10.1126/sciimmunol.aba0178
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Myeloid lncRNA LOUP mediates opposing regulatory effects of RUNX1 and RUNX1-ETO in t(8;21) AML.

    Trinh, Bon Q / Ummarino, Simone / Zhang, Yanzhou / Ebralidze, Alexander K / Bassal, Mahmoud A / Nguyen, Tuan M / Heller, Gerwin / Coffey, Rory / Tenen, Danielle E / van der Kouwe, Emiel / Fabiani, Emiliano / Gurnari, Carmelo / Wu, Chan-Shuo / Angarica, Vladimir Espinosa / Yang, Henry / Chen, Sisi / Zhang, Hong / Thurm, Abby R / Marchi, Francisco /
    Levantini, Elena / Staber, Philipp B / Zhang, Pu / Voso, Maria Teresa / Pandolfi, Pier Paolo / Kobayashi, Susumu S / Chai, Li / Di Ruscio, Annalisa / Tenen, Daniel G

    Blood

    2021  Band 138, Heft 15, Seite(n) 1331–1344

    Abstract: The mechanism underlying cell type-specific gene induction conferred by ubiquitous transcription factors as well as disruptions caused by their chimeric derivatives in leukemia is not well understood. Here, we investigate whether RNAs coordinate with ... ...

    Abstract The mechanism underlying cell type-specific gene induction conferred by ubiquitous transcription factors as well as disruptions caused by their chimeric derivatives in leukemia is not well understood. Here, we investigate whether RNAs coordinate with transcription factors to drive myeloid gene transcription. In an integrated genome-wide approach surveying for gene loci exhibiting concurrent RNA and DNA interactions with the broadly expressed Runt-related transcription factor 1 (RUNX1), we identified the long noncoding RNA (lncRNA) originating from the upstream regulatory element of PU.1 (LOUP). This myeloid-specific and polyadenylated lncRNA induces myeloid differentiation and inhibits cell growth, acting as a transcriptional inducer of the myeloid master regulator PU.1. Mechanistically, LOUP recruits RUNX1 to both the PU.1 enhancer and the promoter, leading to the formation of an active chromatin loop. In t(8;21) acute myeloid leukemia (AML), wherein RUNX1 is fused to ETO, the resulting oncogenic fusion protein, RUNX1-ETO, limits chromatin accessibility at the LOUP locus, causing inhibition of LOUP and PU.1 expression. These findings highlight the important role of the interplay between cell-type-specific RNAs and transcription factors, as well as their oncogenic derivatives in modulating lineage-gene activation and raise the possibility that RNA regulators of transcription factors represent alternative targets for therapeutic development.
    Mesh-Begriff(e) Cell Line, Tumor ; Core Binding Factor Alpha 2 Subunit/genetics ; Gene Expression Regulation, Leukemic ; Humans ; Leukemia, Myeloid, Acute/genetics ; Oncogene Proteins, Fusion/genetics ; RNA, Long Noncoding/genetics ; RUNX1 Translocation Partner 1 Protein/genetics ; Transcriptional Activation
    Chemische Substanzen Core Binding Factor Alpha 2 Subunit ; Oncogene Proteins, Fusion ; RNA, Long Noncoding ; RUNX1 Translocation Partner 1 Protein ; RUNX1 protein, human ; RUNX1T1 protein, human
    Sprache Englisch
    Erscheinungsdatum 2021-05-07
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood.2020007920
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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