Carpo, N.; Tran, V.; Biancotti, J.C.; Cepeda, C.; Espinosa-Jeffrey, A. Space Flight Enhances Stress Pathways in Human Neural Stem Cells. Biomolecules2024, 14, 65.
Carpo, N.; Tran, V.; Biancotti, J.C.; Cepeda, C.; Espinosa-Jeffrey, A. Space Flight Enhances Stress Pathways in Human Neural Stem Cells. Biomolecules 2024, 14, 65.
Carpo, N.; Tran, V.; Biancotti, J.C.; Cepeda, C.; Espinosa-Jeffrey, A. Space Flight Enhances Stress Pathways in Human Neural Stem Cells. Biomolecules2024, 14, 65.
Carpo, N.; Tran, V.; Biancotti, J.C.; Cepeda, C.; Espinosa-Jeffrey, A. Space Flight Enhances Stress Pathways in Human Neural Stem Cells. Biomolecules 2024, 14, 65.
Abstract
Mammalian cells have evolved to function under Earth’s gravity, but how they respond to microgravity remains largely unknown. Neural stem cells (NSCs) are essential for the maintenance of central nervous system (CNS) functions during development and the regeneration of all CNS cell populations. Here, we examined the behavior of space (SPC)-flown NSCs as they readapted to Earth’s gravity. We found that most of these cells survived the space flight and self-renewed. Yet, some showed autophagy-like behaviors (ALB). To ascertain if the secretome from SPC-flown NSCs contained molecules inducing this behavior, we incubated naïve, non-starved NSCs in a medium containing SPC-NSCs secretome. We found a four-fold increase in the ALB rate. Proteomic analysis of the secretome revealed that the protein of highest content produced by SPC-NSCs was secreted protein acidic and rich in cysteine (SPARC), which triggers endoplasmic reticulum (ER) stress leading to lethal ALB. These results offer novel knowledge on the response of neural cells, particularly NSCs, subjected to space microgravity. Moreover, some secreted proteins have been identified as microgravity sensing, paving a new venue for future research aiming at targeting SPARC metabolism. Although we did not establish a direct relationship between ALB and SPARC as a potential marker, these results represent the first step in the identification of gravity sensing molecules as targets to be modulated and to design effective countermeasures to mitigate intracranial hypertension in astronauts using structure-based-protein design.
Keywords
microgravity; space flight; human neural stem cells; autophagy; intracranial hypertension
Subject
Biology and Life Sciences, Neuroscience and Neurology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
