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| Status |
Public on Aug 30, 2022 |
| Title |
Differentiation-related epigenomic changes define clinically distinct keratinocyte cancer subclasses [scRNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Keratinocyte cancers (KC) are the most prevalent malignancies in fair-skinned populations, posing a significant medical and economic burden to health systems. KC originate in the epidermis and mainly comprise basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC). Here, we combined single-cell transcriptomics, methylomics and multi-omics to investigate the epigenomic dynamics during epidermal differentiation. We identified ~4,000 differentially accessible regions between undifferentiated and differentiated keratinocytes, corresponding to regulatory regions associated with key transcription factors. DNA methylation at these regions defined AK/cSCC subtypes with epidermal stem cell- or keratinocyte-like features. Using cell type deconvolution tools and integration of bulk and single-cell methylomes, we demonstrate that these subclasses are consistent with distinct cells-of-origin. Further characterization of the subclasses with an epigenetic mitotic-like clock, and the study of other unstratified KC entities uncovered distinct phenotypic and clinical features for the subclasses, linking invasive and metastatic KC cases with undifferentiated cells-of-origin. Our study provides a thorough characterization of the epigenomic dynamics underlying human keratinocyte differentiation and uncovers novel links between KC cells-of-origin and their prognosis
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| Overall design |
One healthy sun-protected epidermis from the inguinoiliac region from a 30y/o male donor was analysed using the Chromium Single Cell 3’ Reagent Kit, v2 chemistry (10X Genomics).
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| Contributor(s) |
Lyko F, Rodríguez-Paredes M |
| Citation(s) |
36121124 |
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| Submission date |
Jul 01, 2022 |
| Last update date |
Nov 16, 2022 |
| Contact name |
Llorenç Solé Boldo |
| E-mail(s) |
l.sole@DKFZ-heidelberg.de
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| Organization name |
DKFZ
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| Street address |
Im Neuenheimer Feld, 580
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| City |
Heidelberg |
| ZIP/Postal code |
69126 |
| Country |
Germany |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (1) |
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| This SubSeries is part of SuperSeries: |
| GSE207337 |
Differentiation-related epigenomic changes define clinically distinct keratinocyte cancer subclasses |
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| Relations |
| BioProject |
PRJNA854898 |
