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Cell state transitions regulated by Slug are critical for tissue regeneration and tumor initiation

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE54735 | GEO | 2014/06/23

SECONDARY ACCESSION(S): PRJNA237518

REPOSITORIES: GEO

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Cell state transitions regulated by Slug are critical for tissue regeneration and tumor initiation

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-06-23 | E-GEOD-54735 | biostudies-arrayexpress

Cell-state transitions regulated by SLUG are critical for tissue regeneration and tumor initiation.

Project description:Perturbations in stem cell activity and differentiation can lead to developmental defects and cancer. We use an approach involving a quantitative model of cell-state transitions in vitro to gain insights into how SLUG/SNAI2, a key developmental transcription factor, modulates mammary epithelial stem cell activity and differentiation in vivo. In the absence of SLUG, stem cells fail to transition into basal progenitor cells, while existing basal progenitor cells undergo luminal differentiation; together, these changes result in abnormal mammary architecture and defects in tissue function. Furthermore, we show that in the absence of SLUG, mammary stem cell activity necessary for tissue regeneration and cancer initiation is lost. Mechanistically, SLUG regulates differentiation and cellular plasticity by recruiting the chromatin modifier lysine-specific demethylase 1 (LSD1) to promoters of lineage-specific genes to repress transcription. Together, these results demonstrate that SLUG plays a dual role in repressing luminal epithelial differentiation while unlocking stem cell transitions necessary for tumorigenesis.

| S-EPMC4050485 | biostudies-literature

Cell state transitions regulated by Slug are critical for tissue regeneration and tumor initiation [Nanostring nCounter samples]

Project description:Gene expression data of MCF10A cell subpopulations: luminal, basal and luminal. Three samples were analized. Expression of 105 selected genes was evaluated, including 5 HK genes.

2014-06-23 | E-GEOD-51397 | biostudies-arrayexpress

Cell state transitions regulated by Slug are critical for tissue regeneration and tumor initiation [Agilent microarray samples]

Project description:Alterations that perturb differentiation and cell state transitions can lead to defects in development, function and the genesis of cancer. Studying cellular plasticity at high resolution and in real time has proven difficult using existing methods. Here, we use a quantitative approach to gain insights into cell state dynamics of normal mammary epithelial cells (MECs) and validate the model's predictions in vivo. In the absence of Slug/SNAI2, basal mammary progenitor cells transition into a luminal differentiation state, while luminal progenitor cells proliferate and expand; these changes result in abnormal mammary architecture and defects in tissue function. Loss of Slug also disrupts cellular plasticity leading to defects in tissue regeneration and the initiation of cancer. Mechanistically, Slug promotes cellular plasticity by recruiting the chromatin modifier, LSD1 (lysine specific demethylase 1), to promoters of lineage specific genes to represses transcription. Together, these finding demonstrate that Slug is necessary for cellular adaptation during tissue development and regeneration, and that transitioning back into a more primitive stem-like state is a prerequisite for tumor initiation. reference x sample

2014-06-23 | E-GEOD-54713 | biostudies-arrayexpress

Cell state transitions regulated by Slug are critical for tissue regeneration and tumor initiation [Nanostring nCounter samples]

Project description:Gene expression data of MCF10A cell subpopulations: luminal, basal and luminal.

2014-06-23 | GSE51397 | GEO

Cell state transitions regulated by Slug are critical for tissue regeneration and tumor initiation [Agilent microarray samples]

2014-06-23 | GSE54713 | GEO

SLUG Directs the Precursor State of Human Brain Tumor Stem Cells.

Project description:In glioblastoma (GBM), brain tumor stem cells (BTSCs) encompass heterogenous populations of multipotent, self-renewing, and tumorigenic cells, which have been proposed to be at the root of therapeutic resistance and recurrence. While the functional significance of BTSC heterogeneity remains to be fully determined, we previously distinguished relatively quiescent stem-like precursor state from the more aggressive progenitor-like precursor state. In the present study, we hypothesized that progenitor-like BTSCs arise from stem-like precursors through a mesenchymal transition and drive post-treatment recurrence. We first demonstrate that progenitor-like BTSCs display a more mesenchymal transcriptomic profile. Moreover, we show that both mesenchymal GBMs and progenitor-like BTSCs are characterized by over-activated STAT3/EMT pathways and that SLUG is the primary epithelial to mesenchymal transition (EMT) transcription factor directly regulated by STAT3 in BTSCs. SLUG overexpression in BTSCs enhances invasiveness, promotes inflammation, and shortens survival. Importantly, SLUG overexpression in a quiescent stem-like BTSC line enhances tumorigenesis. Finally, we report that recurrence is associated with SLUG-induced transcriptional changes in both BTSCs and GBM patient samples. Collectively, our findings show that a STAT3-driven precursor state transition, mediated by SLUG, may prime BTSCs to initiate more aggressive mesenchymal recurrence. Targeting the STAT3/SLUG pathway may maintain BTSCs in a quiescent stem-like precursor state, delaying recurrence and improving survival in GBM.

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2011 AOA Symposium: Tissue Engineering and Tissue Regeneration: AOA critical issues.

Project description: Not available

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Existence of multiple transitions of the critical state due to anesthetics.

Project description:Scale-free statistics of coordinated neuronal activity, suggesting a universal operating mechanism across spatio-temporal scales, have been proposed as a necessary condition of healthy resting-state brain activity. Recent studies have focused on anesthetic agents to induce distinct neural states in which consciousness is altered to understand the importance of critical dynamics. However, variation in experimental techniques, species, and anesthetics, have made comparisons across studies difficult. Here we conduct a survey of several common anesthetics (isoflurane, pentobarbital, ketamine) at multiple dosages, using calcium wide-field optical imaging of the mouse cortex. We show that while low-dose anesthesia largely preserves scale-free statistics, surgical plane anesthesia induces multiple dynamical modes, most of which do not maintain critical avalanche dynamics. Our findings indicate multiple pathways away from default critical dynamics associated with quiet wakefulness, not only reflecting differences between these common anesthetics but also showing significant variations in individual responses. This is suggestive of a non-trivial relationship between criticality and the underlying state of the subject.

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Chromatin remodeling protein HELLS is critical for retinoblastoma tumor initiation and progression

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

2020-03-09 | GSE144429 | GEO