[PDF][PDF] Renal neoplasms in tuberous sclerosis mice are neurocristopathies

U Unachukwu, T Shiomi, M Goldklang, K Chada… - Iscience, 2021 - cell.com
U Unachukwu, T Shiomi, M Goldklang, K Chada, J D'Armiento
Iscience, 2021cell.com
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 …
Summary
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)/TdTfl/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.
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