Times Single-Cell Sequencing Revealed That IKKα Depletion In Dendritic Cells Related To Spontaneous Tumorigenesis In Mice

Background:Previous studies of our research group found spontaneous tumorigenesis in dendritic cell-specific IKKΑknockout transgenic mice(IKKα^△Itgaxmice).Although the exact mechanism is unclear,it has been recognized that changes in dendritic cells（DC）are the key cause.Therefore,we performed single-cell sequencing on mouse bone marrow derived dendritic cells（BMDC）to look for specific changes in DC.Methods:We first identified the differential genes and possible functional enrichment analysis of mouse BMDC using bulk RNA sequencing（RNA-seq）,and then conducted single-cell RNA sequencing（sc RNA-seq）to further verify the key gene changes and functions changes.Results:Deletion of IKKαin dendritic cells resulted in spontaneous adenocarcinoma in mice,and bulk RNA seq showed that IKKα-deficient dendritic cells had an expression pattern more similar to invasive ductal carcinoma（breast cancer）and that Ccr7 was significantly upregulated.Single-cell sequencing showed that a new dendritic cell subset,the CCR7DC subset,appeared in IKKα^△Itgaxmice after IKKαdeletion,and the proportion of this DC subset was significantly increased.Compared with the classical dendritic cell subsets,which play a key role in antitumor immune responses,the CCR7 DC subsets are less able to induce immune responses and more prone to apoptosis.Therefore,we believe that the immune dysfunctional CCR7 DC subset is one of the key factors in inducing spontaneous tumorigenesis in mice.Conclusion:Deletion of IKKαin dendritic cells impedes the development of dendritic cell precursors and allows them to differentiate into an immunologically dysfunctional CCR7 DC subset.The increased proportion of immune dysfunctional CCR7 DCs is one of the reasons for the spontaneous tumorigenesis in mice.