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

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

PROVIDER: PRJNA788446 | ENA |

REPOSITORIES: ENA

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Activator E2F family transcription factors 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 | GSE190764 | 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

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

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

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

2022-11-01 | GSE190766 | GEO

TRAF6, a master activator of p53 transactivation, suppresses mitochondrial p53 and apoptosis

Project description:TRAF6, a master activator of p53 transactivation, suppresses mitochondrial p53 and apoptosis

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Her2/Neu tumorigenesis and metastasis is regulated by E2F transcription factors

Project description:HER2 / Neu is amplified and overexpressed in a large proportion of human breast cancers, but the signaling pathways that contribute to tumor development and metastatic progression are not completely understood. Using gene expression data and pathway signatures we predicted a role for activator E2F transcription factors in Neu induced tumors. This was genetically tested by interbreeding Neu transgenics with knockouts of the three activator E2Fs. Loss of any E2F delayed Neu induced tumor onset. E2F1 loss accelerated tumor growth while E2F2 and E2F3 loss did not. Strikingly, it was observed that loss of E2F1 or E2F2 significantly reduced the metastatic capacity of the tumor and this was associated with a reduction in circulating tumor cells in the E2F2 knockout. Gene expression analysis between the tumors in the various E2F mutant backgrounds revealed that there was extensive compensation by other E2F family members in the individual knockouts, underscoring the importance of the E2Fs in HER2 / Neu induced tumors. Extension to HER2 positive human breast cancer revealed a number of HER2+ subtypes based on E2F activity with differences in relapse free survival times. Taken together these data demonstrate that the E2F transcription factors are integral to HER2+ tumor development and progression.

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HMEC Quiescent single cells

Project description:Gene expression after mammosphere culture, quiescent single cells

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