A threshold level of NFATc1 activity facilitates thymocyte differentiation and opposes notch-driven leukaemia development.
dc.contributor.author | Patra, AK | |
dc.date.accessioned | 2016-07-20T19:20:02Z | |
dc.date.available | 2016-07-20T19:20:02Z | |
dc.date.issued | 2016-06-17 | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.other | 11841 | |
dc.identifier.uri | http://hdl.handle.net/10026.1/5094 | |
dc.description.abstract |
<jats:title>Abstract</jats:title><jats:p>NFATc1 plays a critical role in double-negative thymocyte survival and differentiation. However, the signals that regulate <jats:italic>Nfatc1</jats:italic> expression are incompletely characterized. Here we show a developmental stage-specific differential expression pattern of <jats:italic>Nfatc1</jats:italic> driven by the distal (P1) or proximal (P2) promoters in thymocytes. Whereas, preTCR-negative thymocytes exhibit only P2 promoter-derived <jats:italic>Nfatc1β</jats:italic> expression, preTCR-positive thymocytes express both <jats:italic>Nfatc1β</jats:italic> and P1 promoter-derived <jats:italic>Nfatc1α</jats:italic> transcripts. Inducing NFATc1α activity from P1 promoter in preTCR-negative thymocytes, in addition to the NFATc1β from P2 promoter impairs thymocyte development resulting in severe T-cell lymphopenia. In addition, we show that NFATc1 activity suppresses the B-lineage potential of immature thymocytes, and consolidates their differentiation to T cells. Further, in the pTCR-positive DN3 cells, a threshold level of NFATc1 activity is vital in facilitating T-cell differentiation and to prevent Notch3-induced T-acute lymphoblastic leukaemia. Altogether, our results show NFATc1 activity is crucial in determining the T-cell fate of thymocytes.</jats:p> | |
dc.format.extent | 11841- | |
dc.format.medium | Electronic | |
dc.language | en | |
dc.language.iso | en | |
dc.publisher | Springer Science and Business Media LLC | |
dc.subject | Animals | |
dc.subject | B-Lymphocytes | |
dc.subject | Cell Differentiation | |
dc.subject | Cell Lineage | |
dc.subject | Cell Survival | |
dc.subject | Gene Expression Regulation, Developmental | |
dc.subject | Lymphopenia | |
dc.subject | Mice | |
dc.subject | Mice, Knockout | |
dc.subject | NFATC Transcription Factors | |
dc.subject | Precursor T-Cell Lymphoblastic Leukemia-Lymphoma | |
dc.subject | Promoter Regions, Genetic | |
dc.subject | Protein Isoforms | |
dc.subject | Receptor, Notch3 | |
dc.subject | Receptors, Antigen, T-Cell | |
dc.subject | Signal Transduction | |
dc.subject | T-Lymphocytes | |
dc.subject | Thymocytes | |
dc.subject | Thymus Gland | |
dc.title | A threshold level of NFATc1 activity facilitates thymocyte differentiation and opposes notch-driven leukaemia development. | |
dc.type | journal-article | |
dc.type | Journal Article | |
dc.type | Research Support, Non-U.S. Gov't | |
plymouth.author-url | https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000379075400001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=11bb513d99f797142bcfeffcc58ea008 | |
plymouth.issue | 1 | |
plymouth.volume | 7 | |
plymouth.publication-status | Published online | |
plymouth.journal | Nature Communications | |
dc.identifier.doi | 10.1038/ncomms11841 | |
plymouth.organisational-group | /Plymouth | |
plymouth.organisational-group | /Plymouth/Faculty of Health | |
plymouth.organisational-group | /Plymouth/Faculty of Health/Peninsula Medical School | |
plymouth.organisational-group | /Plymouth/REF 2021 Researchers by UoA | |
plymouth.organisational-group | /Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine | |
plymouth.organisational-group | /Plymouth/Users by role | |
plymouth.organisational-group | /Plymouth/Users by role/Academics | |
dc.publisher.place | England | |
dcterms.dateAccepted | 2016-05-04 | |
dc.identifier.eissn | 2041-1723 | |
dc.rights.embargoperiod | No embargo | |
rioxxterms.versionofrecord | 10.1038/ncomms11841 | |
rioxxterms.licenseref.uri | http://www.rioxx.net/licenses/all-rights-reserved | |
rioxxterms.licenseref.startdate | 2016-06-17 | |
rioxxterms.type | Journal Article/Review | |
plymouth.oa-location | https://www.nature.com/articles/ncomms11841 |