Identification and Characterization of the Wilms Tumor Cancer Stem Cell

Overview

Journal Adv Sci (Weinh)

Specialty Biomedical Engineering

Date 2023 Apr 28

PMID 37114795

Authors

Astgik Petrosyan

Valentina Villani

Paola Aguiari

Matthew E Thornton

Yizhou Wang

Alex Rajewski

Shengmei Zhou

Paolo Cravedi

Brendan H Grubbs

Roger E De Filippo

Sargis Sedrakyan

Kevin V Lemley

Marie Csete

Stefano Da Sacco

Laura Perin

Affiliations

Soon will be listed here.

Abstract

A nephrogenic progenitor cell (NP) with cancer stem cell characteristics driving Wilms tumor (WT) using spatial transcriptomics, bulk and single cell RNA sequencing, and complementary in vitro and transplantation experiments is identified and characterized. NP from WT samples with NP from the developing human kidney is compared. Cells expressing SIX2 and CITED1 fulfill cancer stem cell criteria by reliably recapitulating WT in transplantation studies. It is shown that self-renewal versus differentiation in SIX2+CITED1+ cells is regulated by the interplay between integrins ITGβ1 and ITGβ4. The spatial transcriptomic analysis defines gene expression maps of SIX2+CITED1+ cells in WT samples and identifies the interactive gene networks involved in WT development. These studies define SIX2+CITED1+ cells as the nephrogenic-like cancer stem cells of WT and points to the renal developmental transcriptome changes as a possible driver in regulating WT formation and progression.

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