NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE228047 Query DataSets for GSE228047
Status Public on Aug 29, 2023
Title ECM composition dictates the mode of cell competition and competence for tumor initiation
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary 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.
 
Overall design FACS isolated keratinocyte CD34- YFP+ cells from K14CreER/Rosa-SmoM2-YFP mouse; FACS isolated keratinocyte CD34- Alpha6+ cells from CD1 mouse (Epidermis) / Separation of dermis by mechanical process from epidermis(Dermis)
 
Contributor(s) Blanpain C, Bansaccal N, Song Y, Sarate R
Citation(s) 37968399
Submission date Mar 23, 2023
Last update date Nov 24, 2023
Contact name Yura Song
E-mail(s) yura.song@ulb.be
Organization name Université Libre de Bruxelles
Lab Laboratory of Stem Cells and Cancer
Street address 808, route de Lennik
City Bruxelles
ZIP/Postal code 1070
Country Belgium
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (8)
GSM7113240 BackSkin Wildtype with GEX library
GSM7113241 BackSkin Wildtype with CellPlex library
GSM7113242 BackSkin SmoM2 induced 3weeks keratinocytes
Relations
BioProject PRJNA947920

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE228047_BackSkin_WT_barcodes.tsv.gz 19.6 Kb (ftp)(http) TSV
GSE228047_BackSkin_WT_features.tsv.gz 254.2 Kb (ftp)(http) TSV
GSE228047_BackSkin_WT_matrix.mtx.gz 15.3 Mb (ftp)(http) MTX
GSE228047_Back_Keratinocytes_WT.rds.gz 154.2 Mb (ftp)(http) RDS
GSE228047_Ear_Keratinocytes_WT.rds.gz 76.7 Mb (ftp)(http) RDS
GSE228047_Ear_WT_barcodes.tsv.gz 14.5 Kb (ftp)(http) TSV
GSE228047_Ear_WT_features.tsv.gz 254.2 Kb (ftp)(http) TSV
GSE228047_Ear_WT_matrix.mtx.gz 14.8 Mb (ftp)(http) MTX
GSE228047_RAW.tar 1.1 Gb (http)(custom) TAR (of MTX, RDS, TSV)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap