GSE117362
Transcriptomic profile of Fanconi anemia (FA) epidermal stem and progenitor cells (ESPCs)
Squamous cell carcinoma (SCC) is a common cancer with global public health burden that arises from ESPCs in the skin or mucosa. To understand how genetic risk factors lay the foundation for SCC and develop effective prevention strategies, it is critical to understand the biology of ESPCs. Extreme predisposition to SCC is a hallmark of FA, an inherited disorder caused by germline loss-of-function mutations in any of 22 genes associated with the FA DNA repair pathway. Although DNA damage is the presumed cause, this does not explain the unique involvement of skin and mucosa as opposed to other solid tissues. To identify new epidermal vulnerabilities beyond DNA damage, we generated the first personalized model of FA epidermis. FA patient-derived induced pluripotent stem cells (PSCs) with a conditional FA pathway (+/-Doxycycline, DOX) were differentiated into ESPCs and 3D epidermis. The goal of this study is to uncover FA-dependent biological processes, performing transcriptome analyses of ESPCs in presence or absence of DOX in monolayer cultures. Overall design: Examination of 2 FA patient-derived ESPC lines with conditional FA pathway (+/-DOX)