Lipid droplet availability affects neural stem/progenitor cell metabolism and proliferation

Nat Commun. 2021 Dec 21;12(1):7362. doi: 10.1038/s41467-021-27365-7.

Abstract

Neural stem/progenitor cells (NSPCs) generate new neurons throughout adulthood. However, the underlying regulatory processes are still not fully understood. Lipid metabolism plays an important role in regulating NSPC activity: build-up of lipids is crucial for NSPC proliferation, whereas break-down of lipids has been shown to regulate NSPC quiescence. Despite their central role for cellular lipid metabolism, the role of lipid droplets (LDs), the lipid storing organelles, in NSPCs remains underexplored. Here we show that LDs are highly abundant in adult mouse NSPCs, and that LD accumulation is significantly altered upon fate changes such as quiescence and differentiation. NSPC proliferation is influenced by the number of LDs, inhibition of LD build-up, breakdown or usage, and the asymmetric inheritance of LDs during mitosis. Furthermore, high LD-containing NSPCs have increased metabolic activity and capacity, but do not suffer from increased oxidative damage. Together, these data indicate an instructive role for LDs in driving NSPC behaviour.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / cytology
  • Astrocytes / metabolism
  • Cell Differentiation
  • Cell Proliferation
  • Gene Expression Regulation
  • Green Fluorescent Proteins / metabolism
  • Inheritance Patterns / genetics
  • Lipid Droplets / metabolism*
  • Lipid Peroxidation
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitosis
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / metabolism*
  • Neurons / cytology
  • Neurons / metabolism
  • Perilipin-2 / metabolism
  • Phospholipids / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reactive Oxygen Species / metabolism

Substances

  • Perilipin-2
  • Phospholipids
  • Plin2 protein, mouse
  • RNA, Messenger
  • Reactive Oxygen Species
  • Green Fluorescent Proteins