Single-cell gene expression profiling reveals functional heterogeneity of undifferentiated human epidermal cells
| Autor: | David W. M. Tan, Matthew Trotter, Kim B. Jensen, Simon Broad, Fiona M. Watt, John T. Connelly |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Keratinocytes
Cellular differentiation Biology Validation Studies as Topic Endocytosis Models Biological Polymerase Chain Reaction Receptor tyrosine kinase Extracellular matrix 03 medical and health sciences Genetic Heterogeneity 0302 clinical medicine Humans Progenitor cell Molecular Biology CD46 Cells Cultured 030304 developmental biology 0303 health sciences Gene knockdown Gene Expression Profiling Stem Cells Cell Differentiation Epithelial Cells Development and Stem Cells Microarray Analysis Molecular biology Cell biology Gene expression profiling Epidermal Cells Delta biology.protein Adhesion Stem cell Epidermis Single-Cell Analysis 030217 neurology & neurosurgery Biomarkers Developmental Biology |
| Zdroj: | Development (Cambridge, England) |
| ISSN: | 1477-9129 |
| Popis: | Human epidermal stem cells express high levels of β1 integrins, delta-like 1 (DLL1) and the EGFR antagonist LRIG1. However, there is cell-to-cell variation in the relative abundance of DLL1 and LRIG1 mRNA transcripts. Single-cell global gene expression profiling showed that undifferentiated cells fell into two clusters delineated by expression of DLL1 and its binding partner syntenin. The DLL1+ cluster had elevated expression of genes associated with endocytosis, integrin-mediated adhesion and receptor tyrosine kinase signalling. Differentially expressed genes were not independently regulated, as overexpression of DLL1 alone or together with LRIG1 led to the upregulation of other genes in the DLL1+ cluster. Overexpression of DLL1 and LRIG1 resulted in enhanced extracellular matrix adhesion and increased caveolin-dependent EGFR endocytosis. Further characterisation of CD46, one of the genes upregulated in the DLL1+ cluster, revealed it to be a novel cell surface marker of human epidermal stem cells. Cells with high endogenous levels of CD46 expressed high levels of β1 integrin and DLL1 and were highly adhesive and clonogenic. Knockdown of CD46 decreased proliferative potential and β1 integrin-mediated adhesion. Thus, the previously unknown heterogeneity revealed by our studies results in differences in the interaction of undifferentiated basal keratinocytes with their environment. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|