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Neural Crest Cell Signatures Drive TSC and LAM Tumorigenesis [human]

GSE292058 Homo sapiens Expression profiling by high throughput sequencing 4 samples Submitted 2026/03/03 Platform GPL24676
Summary
This study was performed to test the hypothesis that neural crest cells (NCCs) are causative cells for multi-systemic neoplasms occurring in Tuberous Sclerosis Complex (TSC) and Lymphangioleiomyomatosis (LAM) disorders. The hypothesis stemmed from the mesenchymal phenotypes of TSC and LAM neoplasms and their occurrence in patients at known ontogenetic destinations for maturing neural crest cells. We determined differential gene expression between single cell populations in wildtype mice renal cortical tissues versus renal cystadenomas of the tuberous sclerosis mice model by RNA sequencing, and validated our findings by immunohistochemistry, RT-qPCR, western blots, and tumorigenicity assays. Based on our results, we pioneer the characterization of cranial NCC-induced tumorigenesis in TSC and LAM and identify the crucial role of novel neurocristopathic markers: secreted phosphoprotein (SPP1) and cytokeratin 18 (Krt18) in disease pathogenesis. Genetic inhibition of Spp1 yields an anti-tumorigenic phenotypes in NCCs.
Published in
Neural crest cell signatures drive tumorigenesis in tuberous sclerosis complex and lymphangioleiomyomatosis
Unachukwu UJ, Garcia EB, Rai N et al. · JCI insight 2026 · PMID 42241577 · doi:10.1172/jci.insight.195013
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Also filed as BioProject PRJNA1236411 and SRA study SRP570583. Searching any of these in the dataset finder brings you back here.

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