Single-keratinocyte transcriptomic analyses identify different clonal types and proliferative potential mediated by FOXM1 in human epidermal stem cells.
Elena EnzoAlessia Secone SeconettiMattia ForcatoElena TenediniMaria Pia PolitoIrene SalaSonia CarulliRoberta ContinClelia PeanoEnrico TagliaficoSilvio BicciatoSergio BondanzaMichele De LucaPublished in: Nature communications (2021)
Autologous epidermal cultures restore a functional epidermis on burned patients. Transgenic epidermal grafts do so also in genetic skin diseases such as Junctional Epidermolysis Bullosa. Clinical success strictly requires an adequate number of epidermal stem cells, detected as holoclone-forming cells, which can be only partially distinguished from the other clonogenic keratinocytes and cannot be prospectively isolated. Here we report that single-cell transcriptome analysis of primary human epidermal cultures identifies categories of genes clearly distinguishing the different keratinocyte clonal types, which are hierarchically organized along a continuous, mainly linear trajectory showing that stem cells sequentially generate progenitors producing terminally differentiated cells. Holoclone-forming cells display stem cell hallmarks as genes regulating DNA repair, chromosome segregation, spindle organization and telomerase activity. Finally, we identify FOXM1 as a YAP-dependent key regulator of epidermal stem cells. These findings improve criteria for measuring stem cells in epidermal cultures, which is an essential feature of the graft.
Keyphrases
- stem cells
- wound healing
- induced apoptosis
- single cell
- genome wide
- dna repair
- cell therapy
- cell cycle arrest
- endothelial cells
- rna seq
- signaling pathway
- endoplasmic reticulum stress
- deep learning
- gene expression
- newly diagnosed
- oxidative stress
- copy number
- cell death
- prognostic factors
- machine learning
- bioinformatics analysis
- pluripotent stem cells
- dna damage response