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<p>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.</p>

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Mechanical impact on neural stem cell lineage decisions in human brain organoids

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月17日

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  • Hanna Lampersperger,
  • Michael Tranchina,
  • Bastian Meth,
  • Dandan Han,
  • Negar Nayebzadeh,
  • Nina Reiter,
  • Sonja Kuth,
  • Markus Lorke,
  • Aldo R Boccaccini,
  • Silvia Budday,
  • Marisa Karow,
  • Sven Falk

摘要

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.