In addition to coordinating the storage and mobilization of neutral fat, lipid droplets (LDs) are conserved organelles that can accommodate additional cargos in order to support animal development. However, it is unclear if each type of cargo is matched with a specific subset of LDs. Here, we report that SEIP-1/seipin defines a subset of oocyte LDs that are required for proper eggshell formation in C. elegans. Using a photoconvertible fluorescent protein-based imaging assay, we found that SEIP-1 positive LDs were selectively depleted after fertilization, coincident of the formation of a lipid-rich permeability barrier of the eggshell. Loss of SEIP-1 function caused impenetrant embryonic arrest, which could be worsened by FAT-3/fatty acyl-CoA desaturase deficiency or suppressed by PLIN-1/Perilipin deficiency. The embryonic development of seip-1; plin-1 mutant in turn depended on the recruitment of RAB-18/Rab18 to LDs, which was not observed in wild type embryos. We propose that SEIP-1 dependent and independent mechanisms act in parallel to ensure the packaging and export of lipid-rich permeability barrier constituents, which involve LDs. The identity of these LDs, as defined by their associated proteins, exhibits unexpected plasticity that ultimately ensures the survival of embryos ex utero.

Tumor staging of upper tract urothelial carcinomas (UTUCs) is relatively difficult to assert accurately before surgery. Here, we used copy number (CN) signatures as a tool to explore their clinical significance of molecular stratification in UTUC. CN signatures were extracted by non-negative matrix factorization from the whole-genome sequencing (WGS) data of 90 Chinese UTUC primary tumor samples. A validation UTUC cohort (n = 56) and a cohort from urinary cell-free DNA (cfDNA) of urothelial cancer patients (n = 94) and matched primary tumors were also examined. Survival analyses were measured using the Kaplan-Meier, and Cox regression was used for multivariate analysis. Here, we identified six CN signatures (Sig1-6). Patients with a high contribution of Sig6 (Sig6high) were associated with higher microsatellite instability level and papillary architecture and had a favorable outcome. Patients with a low weighted genome integrity index were associated with positive lymph node and showed the worst outcome. Sig6high was identified to be an independently prognostic factor. The predictive significance of CN signature was identified by a validation UTUC cohort. CN signatures retained great concordance between primary tumor and urinary cfDNA. In conclusion, our results reveal that CN signature assessment for risk stratification is feasible and provides a basis for clinical studies that evaluate therapeutic interventions and prognosis.