Space Flight Enhances Stress Pathways in Human Neural Stem Cells

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 enhanced stress responses as well as autophagy-like behavior. To ascertain if the secretome from SPC-flown NSCs contained molecules inducing these responses, we incubated naïve, non-starved NSCs in a medium containing SPC-NSC secretome. We found a four-fold increase in stress responses. Proteomic analysis of the secretome revealed that the protein of the highest content produced by SPC-NSCs was secreted protein acidic and rich in cysteine (SPARC), which induces endoplasmic reticulum (ER) stress, resulting in the cell’s demise. 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 the SPARC metabolism. Although we did not establish a direct relationship between microgravity-induced stress 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.

Omics Studies of Tumor Cells under Microgravity Conditions

“…As a result, we are expanding our knowledge more and more about the stay and its effects on humans, animals, microorganisms, bacteria, and cells in space. Simulation experiments and tests in real microgravity (parabolic flights, sounding rocket missions, American Shuttle flights, Russian long-term Foton or Bion and Chinese Shenzhou missions, short-and longterm stays on space stations (Mir, ISS, Chinese space station)) have already increased our knowledge about the dangers of microgravity, cosmic radiation, and other stress factors occurring during and after space missions [238][239][240][241][242][243][244][245][246][247][248][249][250][251][252].…”