Acute kidney injury promotes development of papillary renal cell adenoma and carcinoma from renal progenitor cells

• DOI: 10.1126/scitranslmed.aaw6003
• Publication Date: 2020-03-25T23:09:27Z
• Authors: Anna Julie Peired; Giulia Antonelli; Maria Lucia Angel...; Marco Allinovi; Francesco Guzzi; Alessandro Sisti; Roberto Semeraro; Carolina Conte; Benedetta Mazzinghi; Sara Nardi; Maria Elena Melica; Letizia De Chiara; Elena Lazzeri; Laura Lasagni; Tiziano Lottini; Samuela Landini; Sabrina Giglio; Andrea Mari; Fabrizio Di Maida; Alessandro Antonelli; Francesco Porpiglia; Riccardo Schiavina; Vincenzo Ficarra; Davide Facchiano; Mauro Gacci; Sergio Serni; Marco Carini; George J. Netto; Rosa Maria Roperto; Alberto Magi; Christian Fynbo C...; Mario Rotondi; Helen Liapis; Hans-Joachim Anders; Andrea Minervini; Maria Rosaria Ras...; Paola Romagnani
• Keywords: Renal stem cell; Progenitor; Renal papilla

Acute tissue injury causes DNA damage and repair processes involving increased cell mitosis polyploidization, leading to function alterations that may potentially drive cancer development. Here, we show acute kidney (AKI) the risk for papillary renal carcinoma (pRCC) development tumor relapse in humans as confirmed by data collected from several single-center multicentric studies. Lineage tracing of tubular epithelial cells (TECs) after AKI induction long-term follow-up mice showed time-dependent onset clonal tumors an adenoma-carcinoma sequence. Among AKI-related pathways, NOTCH1 overexpression human pRCC associated with worse outcome was specific type 2 pRCC. Mice overexpressing TECs developed adenomas pRCCs, accelerated this process. identified single progenitors origin tumors. Single-cell RNA sequencing progenitor transcriptome similarities PT1, putative Furthermore, cultured induced tumor-like 3D growth. Thus, can tumorigenesis local cells. In particular, find promotes through a classical