Post-mitotic G1 phase survivin drives mitogen-independent cell divisions of B lymphocytes
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ABSTRACT:
PROVIDER: PRJNA801855 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17818555.fastq.gz | Fastqsanger.gz | |||
| SRR17818556.fastq.gz | Fastqsanger.gz | |||
| SRR17818557.fastq.gz | Fastqsanger.gz | |||
| SRR17818558.fastq.gz | Fastqsanger.gz | |||
| SRR17818559.fastq.gz | Fastqsanger.gz |
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Project description:The prevailing dogma is that renewed mitogenic signaling is essential to traverse G1 phase of the cell cycle after each division. B lymphocytes undergo multiple mitotic divisions, termed clonal expansion, to expand antigen-specific cells that mediate effective immunity. We explored mechanisms by which primary murine B lymphocytes make cell division decisions. We demonstrate that commitment to DNA replication _S phase_ programs B cells to divide multiple times in the absence of overt mitogenic signaling. The extent of division is limited by cell death rather than by return to quiescence, and circumventing cell death permits up to 4 rounds of division in 72h. Mitogen-independent cell cycle progression is driven by unique S- and G2/M- like characteristics of the G1 phase of cells that have divided once, such as, large cell size, low levels of p27, phosphorylated Rb and expression of G2/M markers survivin, Cenp-A and Aim1/Aurora B. Pharmacologic inhibition of survivin blocked G1 progression in a B cell line and in primary B cells undergoing mitogen-independent division. These observations indicate that, in contrast to textbook models of the cell cycle, B cells inherit a partially active G1 phase after cell division that permits them to move quickly to the next S phase in the absence of exogenous G1 progression signals. Our studies provide direct evidence for Pardee’s hypothesis that retention of features of G2/M in post-mitotic cells could trigger a second round of cell cycle progression. We propose that these mechanisms may assist in rapid cell division without differentiation that is required for clonal expansion in response to antigens.
2022-04-29 | GSE195698 | GEO
Project description:B and T lymphocytes of the adaptive immune system undergo proliferative bursts to generate pools of antigen-specific cells for effective immunity. Here we show that in contrast to the canonical view that G1 progression signals are essential after mitosis to reenter S phase, B lymphocytes sustain several rounds of mitogen-independent cell division following the first mitosis. Such division appears to be driven by unique characteristics of the postmitotic G1 phase that has features of S and G2/M phases. Birc5 (survivin), a protein associated with chromosome segregation in G2/M, is expressed in the G1 phase of divided B cells and is necessary for mitogen-independent divisions. The partially active G1 phase and propensity for apoptosis inherited after each division may underlie rapid proliferation and cell death, which are hallmarks of B cell proliferative responses.
| S-EPMC9170024 | biostudies-literature
Project description:Stable inheritance of H3.3-containing nucleosomes during mitotic cell divisions
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Project description:ChIPseq analysis of survivin chromatin binding in activated CD4+ T cells
2022-11-29 | GSE190354 | GEO
Project description:The liver possesses remarkable regenerative capacity in response to injury. Upon partial hepatectomy (PHx), terminally differentiated hepatocytes in the remaining liver enter the cell cycle and restore the liver mass and function within weeks. However, liver regeneration is often impaired in livers with chronic diseases. Survivin, an inhibitor of apoptosis protein (IAP) and member of chromosome passenger complex (CPC), plays versatile roles in cell mitosis and apoptosis. We and others found that the expression of Survivin was highly increased in liver during PHx-induced liver regeneration, which indicated that Survivin played important roles in this process. However, the function of Survivin in liver regeneration remains largely undefined. Here, using mice with genetic deletion of Survivin, we found that during PHx-induced liver regeneration Survivin regulated both hepatocyte G1/S phase transition by inhibiting the expression of p21 and G2/M phase transition by regulating the localization of CPC. Moreover, restoration of Survivin expression in Survivin-deficient hepatocytes inhibited p21 expression and promote both hepatocyte G1/S and G2/M transition during PHx-induced liver regeneration.
2017-01-01 | GSE83598 | GEO
Project description:Background: Survivin was described as strongly expressed in human cancer. To date, little is known about the association between Survivin splice variants and the other apoptosis-related genes. In this study, we analyzed the apoptosis gene signature of Survivin and its variant expression in breast cancer. Methods: Expression of the 5 transcripts was measured by RT-PCR in 135 breast carcinomas. Human Apoptosis Gene Arrays were used to screen the genes that could be associated with Survivin variants. Cox survival analysis was analyzed according to the breast cancer patient outcome. Results: Significant associations between Survivin transcript and the apoptotic gene array were found. Interestingly, Survivin-3B variant showed major inverse correlations with the pro-apoptotic gene array. Overexpression of Survivin-3B strongly inhibits 5-fluorouracil/epirubicin/Cyclophosphamide induced-apoptosis in breast tumor cell lines. In breast carcinomas, uni- and multivariate analysis showed patients with high level of survivin-3B expression had a shorter overall (p=0.030 and p=0.042, respectively) and disease-free (p=0.024 and p=0.009) survival. Conclusion: Our data indicate Survivin-3B could have an anti-apoptotic activity and its expression level might be used as a prognostic marker in breast carcinoma.
2010-10-06 | GSE24556 | GEO
Project description:Background: Survivin was described as strongly expressed in human cancer. To date, little is known about the association between Survivin splice variants and the other apoptosis-related genes. In this study, we analyzed the apoptosis gene signature of Survivin and its variant expression in breast cancer. Methods: Expression of the 5 transcripts was measured by RT-PCR in 135 breast carcinomas. Human Apoptosis Gene Arrays were used to screen the genes that could be associated with Survivin variants. Cox survival analysis was analyzed according to the breast cancer patient outcome. Results: Significant associations between Survivin transcript and the apoptotic gene array were found. Interestingly, Survivin-3B variant showed major inverse correlations with the pro-apoptotic gene array. Overexpression of Survivin-3B strongly inhibits 5-fluorouracil/epirubicin/Cyclophosphamide induced-apoptosis in breast tumor cell lines. In breast carcinomas, uni- and multivariate analysis showed patients with high level of survivin-3B expression had a shorter overall (p=0.030 and p=0.042, respectively) and disease-free (p=0.024 and p=0.009) survival. Conclusion: Our data indicate Survivin-3B could have an anti-apoptotic activity and its expression level might be used as a prognostic marker in breast carcinoma. The expression of 96 apoptosis genes and was analyzed in 41 breast carcinomas and 1 pool of normal mammary tissues. In parallel, every survivin isoform expression was quantified by real-time quantitative PCR. Data obtained with the macro-array were correlated with survivin isoform levels detected by RT-PCR.
2010-10-06 | E-GEOD-24556 | biostudies-arrayexpress
Project description:Transcriptional profiling of human embryonic kidney 293 cells comparing transfected control pEGFP-C1 (empty vector) with pEGFP (survivin vector). One condition experiment; survivin transfected cell as test sample vs empty vector transfected cell as reference; one dye swap replicate
2014-10-21 | E-GEOD-43817 | biostudies-arrayexpress
Project description:Hepatocellular carcinoma (HCC) is a deadly cancer lacking efficacious therapies. Latest studies show that cellular senescence and inflammation play key roles in HCC development, likely reflecting its etiological nature of chronic infection. A better understanding of these intertwined processes would facilitate development of therapies for malignant HCCs. Here, we show that malignant HCCs are drastically reduced after deletion of Survivin, an inhibitor of apoptosis protein. Survivin deficiency induces mitosis defect-caused metabolism reprogram and senescence in HCC cells. Survivin additionally protects both senescent and neighboring non-senescent cancer cells from cell death triggered by senescence-associated inflammatory factor TNFα. Importantly, combination of mitosis inhibitor and pro-apoptosis drug, but not alone, synergistically eliminates HCCs, recapitulating the therapeutic effect of genetic deletion of Survivin. By uncovering the role of Survivin in controlling the interaction of senescence and inflammation responses, our findings propose a strategy for HCC therapy by inducing senescence and boosting TNFα-mediated cell death.
2016-06-22 | GSE64804 | GEO