Dissecting the oncogenic mechanisms of POT1 cancer mutations through deep scanning mutagenesis.

Mutations in the shelterin protein POT1 are associated with diverse cancers, but their role in cancer progression remains unclear. To resolve this, we performed deep scanning mutagenesis in POT1 locally haploid human stem cells to assess the impact of POT1 variants on cellular viability and cancer-associated telomeric phenotypes. Though POT1 is essential, frame-shift mutants are rescued by chemical ATR inhibition, indicating that POT1 is not required for telomere replication or lagging strand synthesis.

iSCORE-PD: an isogenic stem cell collection to research Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder caused by complex genetic and environmental factors. Genome-edited human pluripotent stem cells (hPSCs) offer the uniique potential to advance our understanding of PD etiology by providing disease-relevant cell-types carrying patient mutations along with isogenic control cells. To facilitate this experimental approach, we generated a collection of 55 cell lines genetically engineered to harbor mutations in genes associated with monogenic PD ( A53T, A30P, Ex3del, Q129X, Ex1-5del, G2019S, FS, R498X/FS, c.

Zoledronic acid inhibits TSC2-null cell tumor growth via RhoA/YAP signaling pathway in mouse models of lymphangioleiomyomatosis.

Background: This study is to investigate the effects of zoledronic acid (ZA) on TSC2-null cell proliferation and on the tumor progression and recurrence in mouse models of lymphangioleiomyomatosis (LAM).

Methods: Subcutaneous mouse models and LAM mouse models were established. Immunohistochemistry and immunofluorescence were performed to detect the protein expression levels.