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Robust transcriptional indicators of immune cell death revealed by spatiotemporal transcriptome analyses

Molecular Plant 2022年第6期15卷 1059-1075页

作者： Jose Salguero-Linares Irene Serrano Nerea Ruiz-Solani Marta Salas-Gómez Ujjal Jyoti Phukan Victor Manuel González MartíBernardo-Faura Marc Valls David Rengel Nuria S.Coll Centre for Research in Agricultural Genomics(CRAG) CSIC-IRTA-UAB-UBCampus UABBellaterra08193 BarcelonaSpain LIPM Universitéde ToulouseINRACNRS84195 Castanet-TolosanFrance INRAE GeT-PlaGeGenotoul31326 Castanet-TolosanFrance department of Genetics Universitat de Barcelona08028 BarcelonaSpain Consejo Superior de Investigaciones Científicas(CSIC) BarcelonaSpain department of Plant Molecular Biology and Physiology.Albrechtvon Haller institute for Plant Sciences niversity of GottingenJulia-Lermontowa-Weg3.37077 GottingenGrmany institut de phammacologie et de biologie structurale ipbs Universite deToulouse CNRSUPSBP 64182205 route de Nartxonne310077 Toulouse Cedex 04France

Recognition of a pathogen by the plant immune system often triggers a form of regulated cell death traditionally known as the hypersensitive response(HR).This type of cell death occurs precisely at the site of pathogen recognition,and it is restricted to a few *** research has shed light on how plant immune receptors are mechanistically ***,two central key questions remain largely unresolved:how does cell death zonation take place,and what are the mechanisms that underpin this phenomenon?Consequently,bona fide transcriptional indicators of HR are lacking,which prevents deeper insight into its mechanisms before cell death becomes macroscopic and precludes early or live *** this study,to identify the transcriptional indicators of HR we used the paradigmatic Arabidopsis thaliana–Pseudomonas syringae pathosystem and performed a spatiotemporally resolved gene expression analysis that compared infected cells that will undergo HR upon pathogen recognition with bystander cells that will stay alive and activate *** data revealed unique and time-dependent differences in the repertoire of differentially expressed genes,expression profiles,and biological processes derived from tissue undergoing HR and that of its ***,we generated a pipeline based on concatenated pairwise comparisons between time,zone,and treatment that enabled us to define 13 robust transcriptional HR *** these genes,the promoter of an uncharacterized AAA-ATPase was used to obtain a fluorescent reporter transgenic line that displays a strong spatiotemporally resolved signal specifically in cells that will later undergo pathogen-triggered cell *** valuable set of genes can be used to define cells that are destined to die upon infection with HR-triggering bacteria,opening new avenues for specific and/or high-throughput techniques to study HR processes at a single-cell level.

关键词： Arabidopsis thaliana cell death indicator effector-triggered immunity hypersensitive response pattern-triggered immunity plant immunity Pseudomonas syringae

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Interleukin 7 regulates switch transcription in developing B cells

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Cellular & Molecular Immunology 2021年第3期18卷 776-778页

作者： Audrey Dauba Fatima-Zohra Braikia Chloe Oudinet Ahmed Amine Kham lichi Mnstitut de Pharmacologie et de biologie structurale IPBSUniversite de ToulouseCNRSUniversity Paul Sabatier31077 ToulouseFrance

Class switch recombination(CSR)enables activated mature B cells to change immunoglobulin(Ig)isotype expression from IgM to IgG,IgE,or *** process requires activation-induced cytidine deaminase(AID)expression and transcription of the target sequences at the Ig heavy chain(IgH)constant locus,which is composed of multiple constant(C_(H))genes,each specifying an Ig isotype.

关键词： Interleukin enable IgH

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RIP140 regulates POLK gene expression and the response to alkylating drugs in colon cancer cells

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Cancer Drug Resistance 2022年第2期5卷 401-414页

作者： Pascale Palassin Marion Lapierre Sandrine Bonnet Marie-Jeanne Pillaire Balázs Győrffy Catherine Teyssier Stéphan Jalaguier Jean-Sébastien Hoffmann Vincent Cavaillès Audrey Castet-Nicolas IRCM Institut de Recherche en Cancérologie de MontpellierINSERMU1194Institut Régional du Cancer de MontpellierUniversitéde MontpellierMontpellier 34298France institut de Pharmacologie et de biologie structurale IPBSUniversitéde ToulouseCNRSUPSToulouse 31077France. department of Bioinformatics Semmelweis University and TTK Lendület Cancer Biomarker Research GroupBudapest H-1117Hungary Laboratoire de pathologie Laboratoire d’excellence Toulouse CancerInstitut Universitaire du Cancer-ToulouseOncopoleToulouse 31059France Département de Pharmacie Clinique Centre Hospitalo-Universitaire MontpellierMontpellier 34295France. Unitéde Formation et de Recherche des Sciences Pharmaceutiques et Biologiques Montpellier 34090France.

Aim:The transcription factor RIP140(receptor interacting protein of 140 kDa)is involved in intestinal *** plays a role in the control of microsatellite instability(MSI),through the regulation of MSH2 and MSH6 gene *** aim of this study was to explore its effect on the expression of POLK,the gene encoding the specialized translesion synthesis(TLS)DNA polymeraseκknown to perform accurate DNA synthesis at ***:Different mouse models and engineered human colorectal cancer(CRC)cell lines were used to analyze by RT-qPCR,while Western blotting and luciferase assays were used to elucidate the role of RIP140 on POLK gene *** DNA microarray datasets were *** in vitro sensitivity of CRC cells to methyl methane sulfonate and cisplatin was ***:RIP140 positively regulates,at the transcriptional level,the expression of the POLK gene,and this effect involves,at least partly,the p53 tumor *** different cohorts of CRC biopsies(with or without MSI),a strong positive correlation was observed between RIP140 and POLK gene *** connection with its effect on POLK levels and the TLS function of this polymerase,the cellular response to methyl methane sulfonate was increased in cells lacking the Rip140 ***,the association of RIP140 expression with better overall survival of CRC patients was observed only when the corresponding tumors exhibited low levels of POLK,thus strengthening the functional link between the two genes in human ***:The regulation of POLK gene expression by RIP140 could thus contribute to the maintenance of microsatellite stability,and more generally to the control of genome integrity.

关键词： Colorectal cancer genome stability translesion DNA synthesis polymerase Pol Kappa RIP140

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Tumor cells educate mesenchymal stromal cells to release chemoprotective and immunomodulatory factors

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Journal of Molecular Cell Biology 2020年第3期12卷 202-215页

作者： Augustin Le Naour Melissa Prat Benolt Thibault Renaud Mével Léa Lemaitre Helene Leray Marie-Veronique Joubert Kimberley Coulson Muriel Golzio Lise Lefevre Eliane Mery Alejandra Martinez Gwénael Ferron Jean-Pierre delord Agnès Coste Bettina Couderc institut Claudius Regaud-IUCT Oncopole Universite de ToulouseToulouseFrance INSERM UMR 1037 Cancer Research Center of Toulouse(CRCT)ToulouseFrance UMR 152 Pharma dev Universite de ToulouseIRDUPSToulouseFrance UMR CNRS 5089 Institut de Pharmacologie et de Biologie Structurale(IPBS)ToulouseFrance

Factors released by surrounding cells such as cancer-associated mesenchymal stromal cells(CA-MSCs)are involved in tumor progression and *** this study,we characterize the mechanisms by which naYve mesenchymal stromal cells(MSCs)can acquire a CA-MSCs *** tumor cells trigger the transformation of MSCs to CA-MSCs by expressing pro-tumoral genes implicated in the chemoresistance of cancer cells,resulting in the secretion of high levels of CXC chemokine receptors 1 and 2(CXCR1/2)ligands such as chemokine(C-X-C motif)ligand 1(CXCL1),CXCL2,and interleukin 8(IL-8).CXCR1/2 ligands can also inhibit the immune response against ovarian tumor ***,through their released factors,CA-MSCs promote the differentiation of monocytes towards M2 macrophages,which favors tumor *** CXCR1/2 receptors are inhibited,these CA-MSC-activated macrophages lose their M2 properties and acquire an anti-tumoral *** ex vivo and in vivo,we used a CXCR1/2 inhibitor to sensitize ovarian tumor cells to carboplatin and circumvent the pro-tumoral effects of *** high concentrations of CXCR1/2 ligands in patients*blood are associated with chemoresistance,CXCR1/2 inhibition could be a potential therapeutic strategy to revert carboplatin resistance.

关键词： chemoresistance macrophages mesenchymal stromal cells ovarian adenocarcinoma chemokines

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