Effects of microgravity on neural crest stem cells

Yilin Han; Povilas Barasa; Lukas Zeger; Sara B Salomonsson; Federica Zanotti; Marcel Egli; Barbara Zavan; Martina Trentini; Gunnar Florin; Alf Vaerneus; Håkan Aldskogius; Robert Fredriksson; Elena N Kozlova

doi:10.3389/fnins.2024.1379076

Effects of microgravity on neural crest stem cells

Front Neurosci. 2024 Mar 27:18:1379076. doi: 10.3389/fnins.2024.1379076. eCollection 2024.

Authors

Affiliations

¹ Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
² Institute of Biochemistry, Vilnius University, Vilnius, Lithuania.
³ Department of Pharmaceutical Bioscience, Uppsala University, Uppsala, Sweden.
⁴ Department of Translational Medicine, University of Ferrara, Ferrara, Italy.
⁵ Space Biology Group, School of Engineering and Architecture, Institute of Medical Engineering, Lucerne University of Applied Sciences and Arts, Hergiswil, Switzerland.
⁶ National Center for Biomedical Research in Space, Innovation Cluster Space and Aviation, University of Zurich, Zurich, Switzerland.
⁷ Swedish Space Corporation, Solna, Sweden.

^# Contributed equally.

Abstract

Exposure to microgravity (μg) results in a range of systemic changes in the organism, but may also have beneficial cellular effects. In a previous study we detected increased proliferation capacity and upregulation of genes related to proliferation and survival in boundary cap neural crest stem cells (BC) after MASER14 sounding rocket flight compared to ground-based controls. However, whether these changes were due to μg or hypergravity was not clarified. In the current MASER15 experiment BCs were exposed simultaneously to μg and 1 g conditions provided by an onboard centrifuge. BCs exposed to μg displayed a markedly increased proliferation capacity compared to 1 g on board controls, and genetic analysis of BCs harvested 5 h after flight revealed an upregulation, specifically in μg-exposed BCs, of Zfp462 transcription factor, a key regulator of cell pluripotency and neuronal fate. This was associated with alterations in exosome microRNA content between μg and 1 g exposed MASER15 specimens. Since the specimens from MASER14 were obtained for analysis with 1 week's delay, we examined whether gene expression and exosome content were different compared to the current MASER15 experiments, in which specimens were harvested 5 h after flight. The overall pattern of gene expression was different and Zfp462 expression was down-regulated in MASER14 BC μg compared to directly harvested specimens (MASER15). MicroRNA exosome content was markedly altered in medium harvested with delay compared to directly collected samples. In conclusion, our analysis indicates that even short exposure to μg alters gene expression, leading to increased BC capacity for proliferation and survival, lasting for a long time after μg exposure. With delayed harvest of specimens, a situation which may occur due to special post-flight circumstances, the exosome microRNA content is modified compared to fast specimen harvest, and the direct effects from μg exposure may be partially attenuated, whereas other effects can last for a long time after return to ground conditions.

Keywords: delayed effect; exosomes; gene expression; microRNA; microgravity; neural stem cell; proliferation.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. We were supported by the Swedish National Space Agency (Dnr 2020-00163, 2021-00089) and Åhlens Foundation (Dnr 2022-230).