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Rb family proteins are master regulators of the molecular signatures instructing the quiescent and activated adult neural stem cell state

ABSTRACT: Rb family proteins are master regulators of the molecular signatures instructing the quiescent and activated adult neural stem cell state

PROVIDER: PRJNA788447 | ENA |

REPOSITORIES: ENA

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Rb family proteins are master regulators of the molecular signatures instructing the quiescent and activated adult neural stem cell state

Project description:The long-term maintenance of the adult neurogenic niche and neurogenesis is dependent on the proper regulation of entry and exit from quiescence. The dynamic transition from quiescence to activation is a complex process requiring not only precise cell cycle control, but also a co-ordinated phenotypic transition involving transcriptional and morphological changes. Presently, the mechanisms by which such a complex repertoire of factors interact and co-ordinate with the core cell cycle machinery to mediate these critical NSC fate transitions remains unknown. Here we show that the Rb/E2F axis functions as an on-off switch for NSC quiescence and activation, by linking the cell cycle machinery to pivotal regulators of NSC fate. Compound deletion of Rb family proteins results in massive activation and expansion of NSCs, and induces a global transcriptomic transition towards NSC activation followed by niche depletion. Deletion of their target activator E2Fs1/3 results in the failure of NSCs to become activated and the acquisition of a global transcriptome associated with intractable NSC quiescence and the cessation of adult neurogenesis. We further show that the Rb/E2F axis orchestrates these fate transitions through the direct regulation of factors essential to NSC function, including REST and ASCL1. This places the Rb/E2F axis as a master regulator of NSC fate, coordinating cell cycle control with NSC activation and quiescence fate transitions.

2022-11-01 | GSE190765 | GEO

Rb family proteins and Activator E2F family transcription factors are master regulators of the molecular signatures instructing the quiescent and activated adult neural stem cell state

Project description:Rb family proteins and Activator E2F family transcription factors are master regulators of the molecular signatures instructing the quiescent and activated adult neural stem cell state

| PRJNA788441 | ENA

Activator E2F family transcription factors are master regulators of the molecular signatures instructing the quiescent and activated adult neural stem cell state

2022-11-01 | GSE190764 | GEO

Activator E2F family transcription factors are master regulators of the molecular signatures instructing the quiescent and activated adult neural stem cell state

Project description:Activator E2F family transcription factors are master regulators of the molecular signatures instructing the quiescent and activated adult neural stem cell state

| PRJNA788446 | ENA

Rb family proteins and Activator E2F family transcription factors are master regulators of the molecular signatures instructing the quiescent and activated adult neural stem cell state

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-11-01 | GSE190766 | GEO

Transcription profiling of human IMR90 cells after RNAi suppression of RB, p107 or p130 using in growing, quiescent or ras-induced senescent IMR90 cells

Project description:The action of RB as a tumor suppressor has been difficult to define, in part, due to the redundancy of the related proteins p107 and p130. By coupling advanced RNAi technology to suppress RB, p107 or p130 with a genome wide analysis of gene expression in growing, quiescent or ras-senescent cells, we identified a unique and specific activity of RB in repressing DNA replication as cells exit the cell cycle into senescence, a tumor suppressive program. Experiment Overall Design: Expression profiles of IMR90 cells before and after RNAi-mediated supppression of RB, p107 or p130 in growing, quiescent or ras-induced senescent conditions. RNA was extracted from growing, low serum (0.1% FBS), confluent, or ras-senescent cells.

2010-01-23 | E-GEOD-19864 | biostudies-arrayexpress

Gene expression profiles after RNAi-mediated suppression of RB, p107 or p130 in growing, quiescent or ras-induced senescent IMR90 cells

2010-01-15 | GSE19864 | GEO

TRANSCRIPTIONAL ACTIVATION BY E2F4 INDEPENDENT OF THE RB FAMILY

Project description:E2F transcription factors are central regulators of cell cycle progression and cell fate decisions in mammalian cells. E2F4 is a transcriptional repressor implicated in cell cycle arrest and whose repressive activity depends on its interaction with members of the RB family. E2F4 often represents the predominant E2F activity in cells. Here we show that E2F4 is important for the proliferation and the survival of mouse embryonic stem cells. In these cells, E2F4 acts in part as a transcriptional activator that promotes the expression of cell cycle genes. Importantly, this role for E2F4 is completely independent of the RB family. Accordingly, an unbiased analysis of the E2F4 interactome shows that E2F4 functionally interacts with chromatin regulators associated with gene activation in RB family-mutant cells. Taken together, our findings uncover a non-canonical role for E2F4 that reveal novel insights into the biology of rapidly dividing cell types.

2019-04-26 | PXD008796 | Pride

Genome-wide analysis of RB and p130 binding in human diploid fibroblasts

Project description:The action of RB as a tumor suppressor has been difficult to define, in part, due to the redundancy of the related proteins p107 and p130. By coupling advanced RNAi technology with a genome wide analysis of gene expression and RB chromatin binding, we identified a unique and specific activity of RB in repressing DNA replication as cells exit the cell cycle into senescence, a tumor suppressive program. Binding of RB was examined in growing, quiescent, senescent or senescent cells lackign RB. Binding of p130 was examined in quiescent or senescent cells in the presence or absence of RB. Libraries were prapered from DNA co-precipiated with RB or p130 specific antibodies or from mock (beads-only) immunoprecipiates.

2010-01-15 | E-GEOD-19898 | biostudies-arrayexpress

Expression data from Rb family (Rb, p130 and p107) deficient Hematopoietic stem Cells

Project description:Loss of Rb family in HSCs results in a severe phenotype, such as enhanced proliferation and increase in stem cell number. In addition, HSCs were higly mobilized but failed to transplant. Rb family deficient mice rapidly exhibit a myeloproliferative disease with eosinophilic characteristics. Meanwhile, the lymphoid compartment was severely decreased, due to high apoptotic activity in this lineage. Keywords: unpaired WT versus Rb family deficient KLS

2008-04-25 | GSE11253 | GEO

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