Identification and Characterization of the Wilms Tumor Cancer Stem Cell

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 ITG beta 1 and ITG beta 4. 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.

Automated summary

A nephrogenic progenitor cell (NP) with cancer stem cell characteristics driving Wilms tumor (WT) is identified and characterized using spatial transcriptomics, bulk and single cell RNA sequencing, and complementary in vitro and transplantation experiments. Comparative analysis between NP from WT samples and NP from the developing human kidney reveals that cells expressing SIX2 and CITED1 fulfill cancer stem cell criteria by reliably recapitulating WT in transplantation studies. The interplay between integrins ITG beta 1 and ITG beta 4 regulates self-renewal versus differentiation in SIX2+CITED1+ cells. Spatial transcriptomic analysis defines gene expression maps and identifies interactive gene networks involved in WT development, pointing to the renal developmental transcriptome changes as a possible driver in regulating WT formation and progression.