de Leeuw, J. | Search bioRxiv

bioRxiv2025

A human multilineage gut organoid model for Parkinson disease

Emerging evidence links gut dysfunction to Parkinson disease (PD) pathogenesis, yet human models to study gut-related mechanisms are lacking. We developed a human intestinal organoid model incorporating PD-relevant cell types. Using control and PD patient-derived pluripotent stem cells, we generated intestinal epithelial organoids and vagal neural crest cells, then co-cultured them into assembloids. The resultant structures featured lumen-forming polarized epithelial monolayers with enteroendocrine cells, contractile subepithelial myofibroblast-like layers, and neuroglial networks containing dopaminergic and cholinergic enteric neurons. Notably, assembloids from a PD patient carrying the GBA1-E326K variant exhibited progressive -synuclein accumulation in non-enteroendocrine epithelial cells. This model recapitulates key gut architecture and PD-associated phenotypes, offering a physiologically relevant platform for mechanistic studies and therapeutic discovery targeting gut-brain pathways in PD.

cell biology↗

bioRxiv2019

Wildebeest migration in East Africa: Status, threats and conservation measures

Migration of ungulates is under pressure worldwide from range contraction, habitat loss and degradation, anthropogenic barriers and poaching. Here, we synthesize and compare the extent of historical migrations of the white-bearded wildebeest (Connochaetes taurinus) to their contemporary status, in five premier East African ecosystems, namely the Serengeti-Mara, Masai Mara, Athi-Kaputiei, Amboseli and Tarangire-Manyara. The current status, threats to migration, migratory ranges and routes for wildebeest were characterized using colonial-era maps, literature reviews, GIS and aerial survey databases, GPS collared animals and interviews with long-term researchers. Interference with wildebeest migratory routes and dispersal ranges has stopped or severely threatens continuation of the historical migration patterns in all but the Serengeti-Mara ecosystem where the threat level is relatively lower. Wildebeest migration has collapsed in Athi-Kaputiei ecosystem and is facing enormous pressures from land subdivision, settlements and fences in Amboseli and Mara ecosystems and from cultivation in Tarangire-Manyara ecosystem. Land use change, primarily expansion in agriculture, roads, settlements and fencing, increasingly restrict migratory wildebeest from accessing traditional grazing resources in unprotected lands. Privatization of land tenure in group ranches in Kenya and settlement policy (villagization) in Tanzania have accelerated land subdivision, fencing and growth in permanent settlements, leading to loss of key wildebeest habitats including their migratory routes and wet season calving and feeding grounds. These processes, coupled with increasing human population pressures and climatic variability, are exerting tremendous pressures on wildebeest migrations. Urgent conservation interventions are necessary to conserve and protect the critical wildebeest habitats and migration routes in East Africa.

ecology↗