Project description:iNKT cells are highly conserved innate-like T lymphocytes that develop from CD4+CD8+ DP cells. It remains largely unknown whether post-transcriptional regulation has critical roles in iNKT cells. Here we show conditional deactivation of SRSF1 in DP thymocytes impaired iNKT cell development and survival in a cell-intrinsic manner.
Project description:NSrp70 deficiency (NSRP1f/fCD4Cre) profoundly perturbed the late development of DP thymocytes, leading to a significant reduction of single positive (SP) cells in the thymus and peripheral lymphoid tissues. To gain further insight into how NSrp70 controls thymocyte development from CD69+ DP stage, we performed RNA-seq analysis after sorting CD69+ DP thymocytes from WT and Nsrp1 cKO mice.
Project description:The HIVEP/ZAS/Schnurri genes encode large zinc finger proteins that regulate gene expression through DNA binding to the kappaB motif. The ZAS proteins have also been shown to associate with signaling molecules to regulate the TNFa and TGFb signaling pathways. Because ZAS3 transcript and protein expression is rapidly abrogated in primary lymphocytes upon tissue culture, we have generated a ZAS3-null mouse model to study the physiological function of ZAS3. Mice with targeted disruption of ZAS3 are viable with life span comparable to controls. Additionally, the gross anatomy and histology of the major organs, proliferation rates of splenocytes and thymocytes, and the diversity of the TCRb chains of ZAS3 mice are comparable to wild-type. However, compared to wild-type mice, there are decreased CD3+CD4+ and CD3+CD4+CD69+ thymocyte populations. Additionally, CD44hi/CD62Llo subset and CD25 and CD69 expression are increased in splenocytes of ZAS3 mice. Microarray analysis validated by real time PCR revealed changes in the expression level of specific transcripts in ZAS3-null thymus, including several proteins in the G-protein coupled olfactory receptor family. Furthermore, EMSA shows that disruption of ZAS3 results in varying changes in binding activities towards NF-kB and AP1 binding sites. Other phenotypes observed in the ZAS3 mice include generalized increased bone density in older animals and infertility in females. As with ZAS2/shn-2 mice, disruption of ZAS3 is not lethal and does not grossly affect development or homeostasis. We propose that the ZAS proteins likely have overlapping functions, which may be uncovered with deletion of multiple ZAS genes in a single animal. Keywords: Gene knock-out mouse model
Project description:NSrp70 deficiency (NSRP1f/fCD4Cre) profoundly perturbed the late development of DP thymocytes, leading to a significant reduction of single positive (SP) cells in the thymus and peripheral lymphoid tissues. To gain further insight how NSrp70 controls thymocyte development from DP stage, we performed RNA-seq analysis after sorting DP thymocytes from WT and Nsrp1 cKO mice.
Project description:In thymus, the post-selection single positive thymocytes undergo further intrathymic maturation including down-regulation of CD69 and CD24, up-regulation of Qa-2, through which single positive thymocytes became equipped with emigration competency, then emigrate to periphery. Here we find that RNA binding protein Srsf1 is essential for the final maturation and survival of thymocytes.
Project description:Review on the role of Bcl11b in thymus and periphery and impact on diseases RNA was extracted from DP thymocytes of bcl11bf/fCd4cre/tcra-/- and tcra-/- mice. Tcra-/- mice only have preselected DP thymocytes. Such mice were used to determine the role of Bcl11b before selection, considering the defective positive selection in bcl11bf/fcd4cre mice. RNA was isolated and submitted for library generation and microarray analysis to determine expression profile of bcl11b-/- preselected DP thymocytes.
Project description:To determine Sox4 function during intrathymic αβ T cell development, global transcriptome analysis was performed and suggested a deficit in miR181 expression in Sox4-deficient DP thymocytes.
Project description:T cell-specific deletion of PTEN induces premalignancy in CD4+ CD8+ (DP) immature T cells in the thymus, which progresses to the development of mature CD4+ T cell lymphomas in the lymph nodes and spleen. As part of a screen to identify factors that inhibit progression to malignancy, we compared miRNA expression in premalignant PTEN-deficient DP thymocytes versus wild-type controls.
Project description:T cell-specific deletion of PTEN induces premalignancy in CD4+ CD8+ (DP) immature T cells in the thymus, which progresses to the development of mature CD4+ T cell lymphomas in the lymph nodes and spleen. As part of a screen to identify factors that inhibit progression to malignancy, we compared miRNA expression in premalignant PTEN-deficient DP thymocytes versus wild-type controls. DP thymocytes were collected by cell sorting from three 9-week-old, premalignant T cell-specific PTEN-deficient mice (tPTEN-/-) and three littermate controls. miRNA expression was assessed relative to a reference pool generated from an equal mixture of all samples.
Project description:Skeletal muscle specific SRSF1 KO mice were generated by mating SRSF1flox/flox and MyoD-Cre mice, Total RNA from muscle sample were analyzed by Next Generation Sequencing