Space Flight Enhances Stress Pathways in Human Neural Stem Cells

Area of Science:

• Neuroscience
• Cell Biology
• Space Biology

Background:

• Mammalian cells are adapted to Earth's gravity, but responses to microgravity are poorly understood.
• Neural stem cells (NSCs) are critical for central nervous system (CNS) development and repair.
• Understanding NSC behavior in space is vital for astronaut health and CNS regeneration.

Purpose of the Study:

• To investigate the behavior and adaptive responses of space-flown NSCs upon readaptation to Earth's gravity.
• To determine if the secretome of space-flown NSCs influences naïve NSC responses.
• To identify potential molecular mechanisms and markers of microgravity-induced cellular stress.

Main Methods:

• Culturing and analyzing space-flown NSCs after return to Earth.
• Incubating naïve NSCs with secretome from space-flown NSCs.
• Proteomic analysis of the NSC secretome to identify key proteins.
• Assessing stress responses and endoplasmic reticulum (ER) stress markers.

Main Results:

• Most space-flown NSCs survived and self-renewed, but some exhibited increased stress and autophagy.
• Incubation with space-flown NSC secretome significantly elevated stress responses in naïve NSCs.
• Secreted protein acidic and rich in cysteine (SPARC) was highly abundant in the secretome and induced ER stress, leading to cell death.

Conclusions:

• Space microgravity affects NSC behavior, inducing stress responses and altering their secretome.
• SPARC is identified as a key secreted protein involved in microgravity-induced ER stress.
• These findings open avenues for identifying gravity-sensing molecules and developing countermeasures for spaceflight-related CNS issues.