ECM composition dictates the mode of cell competition and competence for tumor initiation
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA947920 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23948465_1.fastq.gz | Fastqsanger.gz | |||
| SRR23948465_2.fastq.gz | Fastqsanger.gz | |||
| SRR23948466_1.fastq.gz | Fastqsanger.gz | |||
| SRR23948466_2.fastq.gz | Fastqsanger.gz | |||
| SRR23948467_1.fastq.gz | Fastqsanger.gz |
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Project description:The skin epidermis is constantly renewed throughout life. Disruption of the balance between renewal and differentiation can lead to uncontrolled growth and tumor initiation. Basal cell carcinoma (BCC) is the most frequent cancer in human. Cell competition is a biological process that leads to the elimination of cells by winner cells, which have been proposed to be important for tumour initiation. Recent studies identified somatic mutations in cancer drivers in normal tissues that get colonized by clones carrying oncogenic mutations. However, how the different oncogenic mutations impact the balance between renewal and differentiation and lead to clonal expansion, cell competition, tissue colonization and tumor development is currently unknown. Here, using multidisciplinary approaches combining in vivo clonal analysis using intra-vital microscopy, single cell analysis, and functional analysis, we defined at a single cell resolution in living animals how mutations associated with BCC development (SmoM2) affect clonal competition and tumor initiation in real time. We found that SmoM2 expression in the ear epidermis induces a stereotypical pattern of cell competition with clonal expansion leading tumor initiation and invasion. In contrast, SmoM2 expression in the back skin epidermis led to a similar clonal expansion that induces lateral cell competition but without inducing dermal invasion and tumor formation. Single cell analysis showed that oncogene expression is associated with a cellular reprogramming of adult interfollicular cells into embryonic hair follicle progenitor (EHFP) state in the ear but not in the back skin. Comparison between ear and back skin epidermis revealed a very different composition of the dermis with increased stiffness and a denser collagen 1 network in the back skin. Decreasing Collagen 1 expression in the back skin overcame the natural resistance of these cells to undergo EHFP reprogramming and tumor initiation following SmoM2 expression. Altogether our study demonstrates that ECM composition controls the mode of clonal competition and competence to undergo oncogenic transformation upon oncogene expression.
2023-08-29 | GSE228047 | GEO
Project description:The skin epidermis is constantly renewed throughout life1,2. Disruption of the balance between renewal and differentiation can lead to uncontrolled growth and tumour initiation3. Basal cell carcinoma (BCC) is the most frequent cancer in human4,5. Cell competition, the elimination of less fit cells by their neighboring winners, has been proposed to be important for tumour initiation6-10. Recent studies identified somatic mutations in cancer drivers in normal tissues lead to clonal expansion of these mutated cells11-16. However, the ways in which oncogenic mutations impact the balance between renewal and differentiation and lead to clonal expansion, cell competition, tissue colonization and tumour development is currently unknown. Using multidisciplinary approaches which combine lineage tracing, clonal analysis in living animals, single cell sequencing, quantitative proteomics, and functional experiments, we have investigated the mode of cell competition and the ability of oncogene-expressing cells to develop invasive BCC in different skin regions. The quantitative proteomics analysis of the ear and backskin dermis before and 6 weeks after oncogene expression was performed to investigate whether a different composition of the dermis in the ear and the backskin affects the ability of oncogene targeted cells to form BCC. To investigate whether a different composition of the dermis in the ear and the backskin affects the ability of oncogene targeted cells to form BCC, we performed an unbiased quantitative proteomics analysis of the ear and backskin dermis before and 6 weeks after oncogene expression. This analysis revealed that only very few proteins were more highly expressed in the backskin as compared to the ear and included Col1a1 and Col1a2 in WT conditions.
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Project description:we develop an interspecies pluripotent stem cell (PSC) co-culture strategy and uncover a previously unknown mode of cell competition. Interspecies PSC competition occurs during primed but not naive pluripotency, and between evolutionarily distant species. We identified genes related to NF-κB signaling pathways, among others, were upregulated in loser cells and genetic inactivation of RELA, a core component of canonical NF-κB pathway, could overcome interspecies PSC competition. We further showed that an upstream regulator of the NF-κB signaling, MYD88 innate immune signal transduction adaptor, was also involved in promoting loser PSC elimination. Suppressing interspecies PSC competition via genetic perturbation of MYD88 or P65 improved engraftment of human cells in early post-implantation mouse embryos. Our study discovers a new paradigm of cell competition and paves the way for studying evolutionarily conserved cell competition mechanisms during early mammalian development. Strategies developed here to overcome interspecies PSC competition may facilitate interspecies organogenesis between evolutionary distant species, including humans.
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Project description:It is well established that the expression profiles of multiple and possibly redundant matrix remodeling proteases (e.g. collagenases) strongly differentiates in disease and development. Although enzymatic redundancy might be inferred from their close similarity in structure, their in-vivo activity can lead to extremely diverse tissue-remodeling outcomes. We observed that proteolysis of collagen, generated uniquely by individual homologous proteases, leads to a specific cascade of combinatorial events, which eventually affects overall extracellular matrix (ECM) topography, visco-elastic properties and composition. We reveal striking differences in the migratory and signaling patterns, morphology, and gene expression profiles of cells interacting with native collagen-rich ECM matrix degraded by different collagenases. Thus unlike envisioned before degradative matrix remodeling systems are not redundant and give rise to precise ECM-cell crosstalk. As ECM proteolysis is an abundant biochemical process critical to tissue homeostasis these results improve our fundamental understanding of systemic factors dictating cell behavior.
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Project description:This SuperSeries is composed of the following subset Series: GSE36822: Clonal competition with alternating dominance in multiple myeloma [244kCGH] GSE36823: Clonal competition with alternating dominance in multiple myeloma [44kCGH] GSE36824: Clonal competition with alternating dominance in multiple myeloma [GEP] Refer to individual Series
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Project description:This study was designed to look for differential gene expression in the annual dicot weed velvetleaf when it is grown in competition with corn relative to when it is grown in monoculture. Keywords: weed/crop competition
2006-12-06 | GSE6445 | GEO
Project description:Tissue resident macrophages play important roles in tissue homeostasis and repair. However, how macrophages monitor and maintain tissue integrity is not well understood. The extracellular matrix (ECM) is a key structural and organizational component of all tissues. Here, we find that macrophages sense the mechanical properties of the ECM in order to regulate a specific tissue repair program. We show that macrophage mechanosensing is mediated by cytoskeletal remodeling and can be performed in three-dimensional environments through a non-canonical, integrin-independent mechanism analogous to amoeboid migration. We find that these cytoskeletal dynamics also integrate biochemical signaling by CSF1 and ultimately regulate chromatin accessibility to control the mechanosensitive gene expression program. This study suggests a distinct mode of ECM mechanosensing and growth factor signaling through which macrophages may regulate tissue repair and fibrosis.
2024-03-20 | GSE239377 | GEO
Project description:Tissue resident macrophages play important roles in tissue homeostasis and repair. However, how macrophages monitor and maintain tissue integrity is not well understood. The extracellular matrix (ECM) is a key structural and organizational component of all tissues. Here, we find that macrophages sense the mechanical properties of the ECM in order to regulate a specific tissue repair program. We show that macrophage mechanosensing is mediated by cytoskeletal remodeling and can be performed in three-dimensional environments through a non-canonical, integrin-independent mechanism analogous to amoeboid migration. We find that these cytoskeletal dynamics also integrate biochemical signaling by CSF1 and ultimately regulate chromatin accessibility to control the mechanosensitive gene expression program. This study suggests a distinct mode of ECM mechanosensing and growth factor signaling through which macrophages may regulate tissue repair and fibrosis.
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