Renal neoplasms in tuberous sclerosis mice are neurocristopathies

Uchenna Unachukwu; Takayuki Shiomi; Monica Goldklang; Kiran Chada; Jeanine D'Armiento

doi:10.1016/j.isci.2021.102684

Renal neoplasms in tuberous sclerosis mice are neurocristopathies

iScience. 2021 Jun 4;24(7):102684. doi: 10.1016/j.isci.2021.102684. eCollection 2021 Jul 23.

Authors

Uchenna Unachukwu¹, Takayuki Shiomi², Monica Goldklang¹, Kiran Chada³, Jeanine D'Armiento¹

Affiliations

¹ Center for LAM and Rare Lung Disease, Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, 630 West 168 Street, New York, NY 10032, USA.
² Department of Pathology, International University of Health and Welfare, School of Medicine, 4-3 Kouzunomori, Narita-shi, Chiba 286-8686, Japan.
³ Department of Biochemistry, Rutgers-Robert Wood Johnson Medical School, Rutgers University, 675 Hoes Lane, Piscataway, NJ 08854, USA.

Abstract

Tuberous sclerosis (TS) is a rare disorder exhibiting multi-systemic benign neoplasms. We hypothesized the origin of TS neoplastic cells derived from the neural crest given the heterogeneous ecto-mesenchymal phenotype of the most common TS neoplasms. To test this hypothesis, we employed Cre-loxP lineage tracing of myelin protein zero (Mpz)-expressing neural crest cells (NCCs) in spontaneously developing renal tumors of Tsc2 ^+/- /Mpz(Cre)/TdT ^fl/fl reporter mice. In these mice, ectopic renal tumor onset was detected at 4 months of age increasing in volume by 16 months of age with concomitant increase in the subpopulation of tdTomato⁺ NCCs from 0% to 6.45% of the total number of renal tumor cells. Our results suggest that Tsc2 ^+/- mouse renal tumors arise from domiciled proliferative progenitor cell populations of neural crest origin that co-opt tumorigenesis due to mutations in Tsc2 loci. Targeting neural crest antigenic determinants will provide a potential alternative therapeutic approach for TS pathogenesis.

Keywords: cancer;; molecular physiology; stem cells research.

Abstract

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