Identification and Characterization of the Wilms Tumor Cancer Stem Cell

被引:12
作者
Petrosyan, Astgik [1 ,2 ]
Villani, Valentina [1 ]
Aguiari, Paola [1 ,3 ]
Thornton, Matthew E.
Wang, Yizhou [4 ]
Rajewski, Alex [4 ]
Zhou, Shengmei [5 ]
Cravedi, Paolo [6 ,7 ]
Grubbs, Brendan H.
De Filippo, Roger E. [1 ,2 ]
Sedrakyan, Sargis [1 ,2 ]
Lemley, Kevin V. [2 ,8 ]
Csete, Marie [9 ]
Da Sacco, Stefano [1 ,2 ]
Perin, Laura [1 ,2 ]
机构
[1] Childrens Hosp Los Angeles, Saban Res Inst, Div Urol, GOFARR Lab, Los Angeles, CA 90027 USA
[2] Univ Southern Calif, Keck Sch Med, Los Angeles, CA 90033 USA
[3] Univ Calif Los Angeles, David Geffen Sch Med, VA Healthcare Syst, Los Angeles, CA 90095 USA
[4] Cedars Sinai Med Ctr, Dept Biomed Sci, Genom Core, Los Angeles, CA 90048 USA
[5] Childrens Hosp Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90027 USA
[6] Icahn Sch Med Mt Sinai, Recanati Miller Transplant Inst, Dept Med, Div Nephrol, New York, NY 10029 USA
[7] Icahn Sch Med Mt Sinai, Recanati Miller Transplant Inst, Translat Transplant Res Ctr, New York, NY 10029 USA
[8] Univ Southern Calif, Childrens Hosp Los Angeles, Dept Pediat, Div Nephrol, Los Angeles, CA 90027 USA
[9] Univ Southern Calif, Dept Anesthesiol, Los Angeles, CA 90033 USA
关键词
cancer; nephron progenitors; Wilms tumor; LAMININ-BINDING INTEGRINS; EXTRACELLULAR-MATRIX; MOLECULAR REGULATION; KIDNEY DEVELOPMENT; EXPRESSION; DIFFERENTIATION; ELEMENTS; MARKERS; CITED1; SIX2;
D O I
10.1002/advs.202206787
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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.
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页数:19
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