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

Romero-Wolf, Maile and Shin, Boyoung and Zhou, Wen and Koizumi, Maria and Rothenberg, Ellen V. and Hosokawa, Hiroyuki (2020) Notch2 complements Notch1 to mediate inductive signaling that initiates early T cell development. Journal of Cell Biology, 219 (10). Art. No. e202005093. ISSN 0021-9525. https://resolver.caltech.edu/CaltechAUTHORS:20200805-124144469

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Abstract

Notch signaling is the dominant intercellular signaling input during the earliest stages of T cell development in the thymus. Although Notch1 is known to be indispensable, we show that it does not mediate all Notch signaling in precommitment stages: Notch2 initially works in parallel to promote early murine T cell development and antagonize other fates. Notch-regulated target genes before and after T lineage commitment change dynamically, and we show that this partially reflects shifts in genome-wide DNA binding by RBPJ, the transcription factor activated by complex formation with the Notch intracellular domain. Although Notch signaling and transcription factor PU.1 can activate some common targets in precommitment T progenitors, Notch signaling and PU.1 activity have functionally antagonistic effects on multiple targets, delineating separation of pro-T cells from alternative PU.1-dependent fates. These results define a distinct mechanism of Notch signal response that distinguishes the initial stages of murine T cell development.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1083/jcb.202005093DOIArticle
ORCID:
AuthorORCID
Romero-Wolf, Maile0000-0002-8024-7198
Zhou, Wen0000-0003-0357-2744
Koizumi, Maria0000-0001-8275-5594
Rothenberg, Ellen V.0000-0002-3901-347X
Hosokawa, Hiroyuki0000-0002-9592-2889
Additional Information:© 2020 Romero-Wolf et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). Submitted: 13 May 2020; Revised: 7 July 2020; Accepted: 9 July 2020. This work was supported by grants to E.V. Rothenberg from the U.S. Public Health Service (R01AI135200, R01AI083514, and R01HD076915) and by grants to H. Hosokawa from the Japan Society for the Promotion of Science (KAKENHI grant JP19H03692), the Mochida Memorial Foundation for Medical and Pharmaceutical Research, the Naito Foundation, and the Takeda Science Foundation. Support was also received by M. Romero-Wolf from the California Institute for Regenerative Medicine Bridges to Stem Cell Research Program (Pasadena City College and California Institute of Technology) and by E.V. Rothenberg from the Louis A. Garfinkle Memorial Laboratory Fund, the Al Sherman Foundation, and the Albert Billings Ruddock Professorship. The authors declare no competing financial interests. Author contributions: M. Romero-Wolf designed the study, performed experiments, analyzed data, and wrote the manuscript. B. Shin performed experiments, analyzed data, and edited the manuscript. W. Zhou analyzed data and edited the manuscript. M. Koizumi performed experiments and analyzed data. E.V. Rothenberg designed and supervised the study, analyzed data, and wrote the manuscript. H. Hosokawa designed and supervised the study, performed experiments, analyzed data, and wrote the manuscript.
Funders:
Funding AgencyGrant Number
NIHR01AI135200
NIHR01AI083514
NIHR01HD076915
Japan Society for the Promotion of Science (JSPS)JP19H03692
Mochida Memorial FoundationUNSPECIFIED
Naito FoundationUNSPECIFIED
Takeda Science FoundationUNSPECIFIED
California Institute for Regenerative Medicine (CIRM)UNSPECIFIED
Louis A. Garfinkle Memorial Laboratory FundUNSPECIFIED
Al Sherman FoundationUNSPECIFIED
Albert Billings Ruddock ProfessorshipUNSPECIFIED
Subject Keywords:Cell signaling, Chromatin or epigenetics, Development, Immunology
Issue or Number:10
Record Number:CaltechAUTHORS:20200805-124144469
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200805-124144469
Official Citation:Maile Romero-Wolf, Boyoung Shin, Wen Zhou, Maria Koizumi, Ellen V. Rothenberg, Hiroyuki Hosokawa; Notch2 complements Notch1 to mediate inductive signaling that initiates early T cell development. J Cell Biol 5 October 2020; 219 (10): e202005093. doi: https://doi.org/10.1083/jcb.202005093
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:104761
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:05 Aug 2020 19:52
Last Modified:05 Aug 2020 19:52

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