MRNA destabilization by BTG1 and BTG2 maintains T cell quiescence
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA517898 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:mRNA destabilization by BTG1 and BTG2 maintains T cell quiescence [mTAIL-seq]
| PRJNA517899 | ENA
Project description:mRNA destabilization by BTG1 and BTG2 maintains T cell quiescence [RNA-seq]
| PRJNA517726 | ENA
Project description:Quiescence is a cellular state in which cells undergo reversible cell cycle arrest in response to environmental challenges or lack of stimuli. When favourable conditions are engaged, the cells exit quiescence and start to proliferate. For example, quiescent stem cells and oocytes are activated by differentiation signals and fertilization, respectively. The regulation of quiescent state is also crucial for lymphocytes, such as T cells. Inappropriate activation of T cells often leads to autoimmune diseases and thus, the balance between quiescent and activated T cells must be preserved. Despite its importance, however, how T cells maintain the ‘quiescent state’ and exit from it remain largely unknown. Here, we identify BTG1 and BTG2 (BTG1/2) as factors responsible for T cell quiescence. Knockout of Btg1/2 in T cells resulted in a reduced threshold to T cell activation, increased proliferation and a concomitant reduction of the frequency of naive T cells. Loss of BTG1/2 rendered naive T cells to become spontaneously activated even without TCR stimuli. Interestingly, we found a global increase in mRNA abundance in naive T cells that lack BTG1/2. In addition, depletion of BTG1/2 led to an increase in mRNA half-life and poly(A) tail length. Thus, BTG1/2 promotes deadenylation and degradation of mRNA in naive T cells. Our study demonstrates a key mechanism underlying T cell quiescence, and suggests low mRNA abundance as a key feature for maintaining quiescent T cells.
2020-01-31 | GSE125889 | GEO
Project description:Quiescence is a cellular state in which cells undergo reversible cell cycle arrest in response to environmental challenges or lack of stimuli. When favorable conditions are engaged, the cells exit quiescence and start to proliferate. For example, quiescent stem cells and oocytes are activated by differentiation signals and fertilization, respectively. The regulation of quiescent state is also crucial for lymphocytes, such as T cells. Inappropriate activation of T cells often leads to autoimmune diseases and thus, the balance between quiescent and activated T cells must be preserved. Despite its importance, however, how T cells maintain the ‘quiescent state’ and exit from it remain largely unknown. Here, we identify BTG1 and BTG2 (BTG1/2) as factors responsible for T cell quiescence. Knockout of Btg1/2 in T cells resulted in a reduced threshold to T cell activation, increased proliferation and a concomitant reduction of the frequency of naive T cells. Loss of BTG1/2 rendered naive T cells to become spontaneously activated even without TCR stimuli. Interestingly, we found a global increase in mRNA abundance in naive T cells that lack BTG1/2. In addition, depletion of BTG1/2 led to an increase in mRNA half-life and poly(A) tail length. Thus, BTG1/2 promotes deadenylation and degradation of mRNA in naive T cells. Our study demonstrates a key mechanism underlying T cell quiescence, and suggests low mRNA abundance as a key feature for maintaining quiescent T cells.
2020-01-31 | GSE125865 | GEO
Project description:The human BTG1 and BTG2 genes are targeted by genetic alterations in hematological malignancies. In this study we examined the unique and overlapping functions of Btg1 and Btg2 in mouse B cell development. Mice deficient for Btg1 and Btg2 displayed the strongest phenotype with a decrease in B cell numbers in bone marrow due to impaired B cell commitment and immature B cell differentiation. To determine the underlying mechanism, microarray expression analyis was performed on early (B220+ CD43+) and late (B220+ CD43-) B cells of WT and Btg1;Btg2 dKO mice. Total RNA obtained from sorted B220+ CD43+ ( Hardy fractions ABC) and B220+ CD43- (Hardy fractions DEF) BM cells of WT and Btg1-/-;Btg2-/- mice. In total 4 samples were analyzed and no replicates were included.
2014-03-19 | E-GEOD-55997 | biostudies-arrayexpress
Project description:The human BTG1 and BTG2 genes are targeted by genetic alterations in hematological malignancies. In this study we examined the unique and overlapping functions of Btg1 and Btg2 in mouse B cell development. Mice deficient for Btg1 and Btg2 displayed the strongest phenotype with a decrease in B cell numbers in bone marrow due to impaired B cell commitment and immature B cell differentiation. To determine the underlying mechanism, microarray expression analyis was performed on early (B220+ CD43+) and late (B220+ CD43-) B cells of WT and Btg1;Btg2 dKO mice.
2014-03-19 | GSE55997 | GEO
Project description:Id4 maintains quiescence of adult hippocampal stem cells
| PRJNA480836 | ENA
Project description:Quiescence is essential for the long term maintenance of adult stem cells and tissue homeostasis. However, how stem cells maintain quiescence is still poorly understood. Here we show that stem cells in the dentate gyrus of the adult hippocampus actively transcribe the proactivation factor Ascl1 regardless of their activation state. We found that the inhibitor of DNA binding protein Id4 suppresses Ascl1 activity in neural stem cell cultures. Id4 sequesters Ascl1 heterodimerisation partner, promoting the degradation of Ascl1 protein and neural stem cell quiescence. Accordingly, elimination of Id4 from stem cells in the adult hippocampus results in abnormal accumulation of Ascl1 protein and premature stem cell activation. We also found that multiple signalling pathways converge on the regulation of Id4 to control the activity of hippocampal stem cells. Id4 therefore maintains quiescence of adult neural stem cells, in sharp contrast with its role of promoting the proliferation of embryonic neural progenitors.
2019-10-18 | GSE116997 | GEO
Project description:Tubastatin A maintains skeletal muscle stem cell (MuSC) quiescence
| PRJNA737274 | ENA
Project description:Total RNA was isolated from n=3 culture wells per siRNA treatment group, from 6 independent primary neonatal rat cardiomyocyte isolations. RNA was pooled to obtain n=3 independent samples per siRNA treatment group for sequencing. The siRNA treatment groups were= siScr (Scramble control), siBtg12 (Btg1/Btg2 double knockdown), siBtg1 (Btg1 single knockdown), siBtg2 (Btg2 single knockdown).
2023-05-24 | GSE203493 | GEO