Biology subjects

Yerly, L.

Publications and source records attributed to Yerly, L..

2 recordsLinked to original sources

bioRxiv2024

Wounding triggers invasive progression in human basal cell carcinoma

The interconnection between wound healing and cancer has long been recognized, as epitomized by the expression "cancer is a wound that does not heal". However, the impact of inducing a wound, such as through biopsy collection, on the progression of established tumors remains largely unknown. In this study, we apply single-cell spatial transcriptomics to characterize the heterogeneity of human basal cell carcinoma (BCC) and identify a wound response gene program as the most prominent feature of highly invasive BCC. To explore the causal relationship between wounding and cancer invasive progression, we perform a longitudinal experiment to compare human tumors at baseline and one week post-biopsy. Our results demonstrate that biopsy collection triggers, in proximity of the wound, the same transcriptional cancer cell state observed in highly invasive BCC. This cancer cell transcriptional switch is coupled with morphological changes and the transcriptional reprogramming of cancer-associated fibroblasts (CAFs). This study provides evidence that wounding triggers invasive progression of established human tumors and warrants further research on the potentially harmful effects of biopsies and wound-inducing treatments.

cancer biology↗

bioRxiv2021

Naive and in vitro-activated primary mouse CD8+ T cells retain in vivo immune responsiveness after electroporation-based CRISPR/Cas9 genetic engineering

CRISPR/Cas9 technology has revolutionized genetic engineering of primary cells. Although its use is gaining momentum in studies on CD8+ T cell biology, it remains elusive to what extent CRISPR/Cas9 affects in vivo function of CD8+ T cells. Here, we optimized nucleofection-based CRISPR/Cas9 genetic engineering of naive and in vitro-activated primary mouse CD8+ T cells and tested their in vivo immune responses. Nucleofection of naive CD8+ T cells preserved their in vivo antiviral immune responsiveness to an extent that is indistinguishable from non-nucleofected cells, whereas in vitro activation of CD8+ T cells prior to nucleofection led to slightly impaired expansion/survival. Of note, different target proteins displayed distinct decay rates after gene editing. This is in stark contrast to a comparable period of time required to complete gene inactivation. Thus, for optimal experimental design, it is crucial to determine the kinetics of the loss of target gene product to adapt incubation period after gene editing. In sum, nucleofection-based CRISPR/Cas9 genome editing achieves efficient and rapid generation of mutant CD8+ T cells without imposing detrimental constraints on their in vivo functions.

immunology↗