Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

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

ABSTRACT: 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

ORGANISM(S): Homo sapiens

SUBMITTER: Charles Perou

PROVIDER: E-GEOD-54713 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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

Phillips Sarah S Prat Aleix A Sedic Maja M Proia Theresa T Wronski Ania A Mazumdar Sohini S Skibinski Adam A Shirley Stephanie H SH Perou Charles M CM Gill Grace G Gupta Piyush B PB Kuperwasser Charlotte C

Stem cell reports 20140424 5

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; to ...[more]

PMID: 24936451

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Dataset Information

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

Publications

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

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