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Gene expression change of MDCK cells expressing scribble shRNA in a tetracycline-inducible manner (scribKD cells)

ABSTRACT: Cell competition is a social cellular phenomenon in which unfit cells are selectively eliminated by wild-type (WT) cells. Although recent studies show that mechanical forces induce competitive cell-cell interactions, it remains largely unknown how unfit cells are sensed and mechanically eliminated. Here, we report that MDCK cells depleted of the polarity gene scribble (scribKD cells) secrete FGF21 to drive cell competition. Knockdown of FGF21 in scribKD cells or loss of FGFR1 in WT cells increases the survival rate of scribKD cells in cell competition, suggesting that WT cells recognize scribKD cells through FGF21. Moreover, FGF21 promotes the compression and elimination of scribKD cells by attracting surrounding WT cells. We also demonstrate that activation of the ASK1-p38 pathway in scribKD cells induces FGF21 to drive cell competition. Our findings reveal a mechanism whereby WT cells mechanically eliminate scribKD cells and propose a new function for FGF21 in cell-cell communication. We performed DNA microarray analysis to search for the genes responsible for cell competition.

ORGANISM(S): Canis lupus familiaris

PROVIDER: GSE153186 | GEO | 2020/12/22

REPOSITORIES: GEO

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Gene expression profile of cells with unfit Wnt morphogen gradient during cell competition

Project description:Morphogen signalling forms an activity gradient and instructs cell identities in a signalling strength-dependent manner to pattern developing tissues. However, developing tissues also undergo dynamic morphogenesis, which may produce cells with unfit morphogen signalling and consequent noisy morphogen gradient. Here we show that a cell competition-related system corrects such noisy morphogen gradients. Zebrafish imaging analyses of the Wnt/β-catenin signalling gradient, which acts as a morphogen to establish embryonic anterior-posterior patterning, revealed that unfit cells with abnormal Wnt/β-catenin activity spontaneously appear and produce noise in the gradient. Communication between unfit and neighbouring fit cells via cadherin proteins stimulates apoptosis of the unfit cells by activating Smad signalling and reactive oxygen species production. This unfit cell elimination is required for proper Wnt/β-catenin gradient formation and consequent anterior-posterior patterning. Because this gradient controls patterning not only in the embryo but also in adult tissues, this system may support tissue robustness and disease prevention.

2019-09-15 | GSE133526 | GEO

Gene expression profile of cells with unfit Wnt morphogen gradient during cell competition

Project description:Gene expression profile of cells with unfit Wnt morphogen gradient during cell competition

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Gene expression signatures of MDCK-pTR GFP-RasV12 mCherry-β-catenin Δ131 cells cultured alone or mixed with MDCK mCherry-β-catenin Δ131 cells

Project description:Normal epithelial cells exert their competitive advantage over RasV12-transformed cells and eliminate them into apical lumen via cell competition. However, it remains elusive which internal or external factors compromise cell competition and provoke oncogenesis. Here, we examine the effect of sequential accumulation of gene mutations mimicking multi-sequential carcinogenesis on RasV12-induced cell competition. Consequently, we find that directionality of cell extrusion of RasV12 cells mosaically produced within Wnt-activated epithelia is reversed, and transformed cells are delaminated into basal lamina via non-cell autonomous MMP21 upregulation. Elevated production of MMP21 is elicited partly through NF-κB signaling, which blockage restores apical elimination of RasV12 cells. Collectively, this study demonstrates that cells with high mutational burdens exploit cell competition for their benefit by behaving as unfit cells and are endowed with an invasion advantage. We performed microarray analysis to search for molecules whose expression is changed in β-catenin Δ131/RasV12 cells surrounded by β-catenin Δ131 cells.

2022-11-16 | GSE217830 | GEO

Identifying genes differentially expressed in MDCK cells with scribble knock-down (scribKD)

Project description:Aim: To identify genes and pathways involved in elimination of scribKD cells by competition. Methods: We carried out mRNA sequencing of MDCK-II cells carrying a tetracycline-inducible scribble shRNA construct.

2017-02-09 | GSE79042 | GEO

Fibroblast growth factor 21 ameliorates cholestatic liver injury via a hepatic FGFR4-JNK pathway

Project description:Cholestasis is characterized by hepatic accumulation of cytotoxic bile acids (BAs), which often subsequentlyleads to liver injury, inflammation, fibrosis, and ultimately liver cirrhosis. Fibroblast growth factor 21 (FGF21) is a liver secreted hormone with pleiotropic effects on the homeostasis of glucose, lipid, and energy metabolism. However, whether hepatic FGF21 plays a role in cholestatic liver injury remains elusive. We found that serum and hepatic FGF21 levels were significantly increased in response to cholestatic liver injury. Hepatocyte-specific deletion of Fgf21 exacerbated hepatic accumulation of BAs, further accentuating liver injury. Consistently, administration of rFGF21 ameliorated cholestatic liver injury in α-naphthylisothiocyanate (ANIT)-treated and Mdr2 deficiency mice. Mechanically, FGF21 activated a hepatic FGFR4-JNK signaling pathway to decrease Cyp7a1 expression, thereby reducing hepatic BAs pool. Our study demonstrates that hepatic FGF21 functions as an adaptive stress-responsive signal to downregulate BA biosynthesis, thereby ameliorating cholestatic liver injury, and FGF21 analogs may represent a candidate therapy for cholestatic liver diseases.

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The role of FGF21 in the effects of low protein diet on the transcriptome of aged mouse kidneys

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2021-10-27 | GSE162967 | GEO

Elucidating the role of UCP1 and FGF21 for metabolic homeostasis in the cold

Project description:Global RNA sequencing analysis of the hypothalamus, BAT, inguinal WAT and muscle of long-term cold exposed WT, FGF21 KO, UCP1 KO and UCP1/FGF21 double KO mice

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Impact of UCP1 and FGF21 for the development of diet-induced obesity at standard housing temperatures

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2019-11-05 | GSE122167 | GEO

Young human glial progenitor cells outcompete and replace older and diseased human cells when transplanted into adult human glial chimeric mice

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2023-04-04 | GSE206322 | GEO

Profile of Bmpr1a-/- embryonic stem cells in ESC media and N2B27

Project description:A fundamental question in developmental biology is whether there are mechanisms to detect stem cells with mutations that although do not adversely affect their viability, would compromise their ability to contribute to further development. Here we show that cell competition is a novel mechanism regulating the fitness of embryonic stem cells (ESCs). We find that ESCs displaying defective BMP signalling, defective autophagy or are tetraploid are eliminated at the onset of differentiation by wild-type cells. This elimination occurs in an apoptotic dependent manner and is mediated by secreted factors. Furthermore, during this process we find that establishment of differential cMyc levels is critical and that cMyc over-expression is sufficient to induce competitive behaviour in ESCs. Cell competition is therefore a process that allows recognition and elimination of defective cells during the early stages of development and is likely to play important roles in tissue homeostasis and stem cell maintenance. We used microarrays to compare the gene expression profiles of Bmpr1a-/- and control embryonic stem cells (ESCs) in the ESC state and after differentiation in N2B27 Microarray profiles of control and Bmpr1a-/- mouse embryonic stem cells in embryonic stem cell culture media and in N2B27

2013-06-20 | E-GEOD-48092 | biostudies-arrayexpress

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