Mechanical impact on neural stem cell lineage decisions in human brain organoids
Summary
During neurodevelopment neural stem cells give rise to a spatially patterned tissue in which a regionally differentially regulated balance between proliferation and differentiation produces the fine-tuned number of neurons and macroglia necessary for a functional central nervous system. The cells driving these highly intricated developmental processes of patterning, growth and differentiation are constantly exposed to a mechanical environment that is, however, variable between different brain regions and along differentiation trajectories. Here we demonstrate that both, acute mechanical manipulations as well as a persistent change in the mechanical environment provided to human brain organoids, instruct neural stem cell lineage decisions. Furthermore, we dissect the underlying changes in the molecular program of organoid-resident cells by bulk- and single cell RNA-sequencing. These data reveal that mechanical manipulations impact on molecular programs governing early patterning events as well as cell-type-specific cellular metabolism. Thus, our results unravel a regulatory network linking mechanics and neural stem cell lineage decisions. © 2026. The Author(s).
| Authors | Lampersperger H, Tranchina M, Meth B, Han D, Nayebzadeh N, Reiter N, Kuth S, Lorke M, Boccaccini AR, Budday S, Karow M, Falk S |
|---|---|
| Journal | EMBO reports |
| Publication Date | 2026 Mar;27(6):1393-1413 |
| PubMed | 41703074 |
| PubMed Central | PMC13022303 |
| DOI | 10.1038/s44319-026-00719-2 |