Space Flight Enhances Stress Pathways in Human Neural Stem Cells
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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-01-01
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| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/14/1/65 |
| _version_ | 1797344568484560896 |
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| author | Nicholas Carpo Victoria Tran Juan Carlos Biancotti Carlos Cepeda Araceli Espinosa-Jeffrey |
| author_facet | Nicholas Carpo Victoria Tran Juan Carlos Biancotti Carlos Cepeda Araceli Espinosa-Jeffrey |
| author_sort | Nicholas Carpo |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T11:04:36Z |
| format | Article |
| id | doaj.art-a83c72a8d17141bdaf314597148af5c0 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-08T11:04:36Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-a83c72a8d17141bdaf314597148af5c02024-01-26T15:19:10ZengMDPI AGBiomolecules2218-273X2024-01-011416510.3390/biom14010065Space Flight Enhances Stress Pathways in Human Neural Stem CellsNicholas Carpo0Victoria Tran1Juan Carlos Biancotti2Carlos Cepeda3Araceli Espinosa-Jeffrey4Department of Psychiatry, UCLA, Los Angeles, CA 90095, USADepartment of Psychiatry, UCLA, Los Angeles, CA 90095, USADepartment of Surgery, Division of Pediatric Surgery, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USADepartment of Psychiatry, UCLA, Los Angeles, CA 90095, USADepartment of Psychiatry, UCLA, Los Angeles, CA 90095, USAMammalian 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.https://www.mdpi.com/2218-273X/14/1/65microgravityspace flighthuman neural stem cellscell stressintracranial hypertension |
| spellingShingle | Nicholas Carpo Victoria Tran Juan Carlos Biancotti Carlos Cepeda Araceli Espinosa-Jeffrey Space Flight Enhances Stress Pathways in Human Neural Stem Cells Biomolecules microgravity space flight human neural stem cells cell stress intracranial hypertension |
| title | Space Flight Enhances Stress Pathways in Human Neural Stem Cells |
| title_full | Space Flight Enhances Stress Pathways in Human Neural Stem Cells |
| title_fullStr | Space Flight Enhances Stress Pathways in Human Neural Stem Cells |
| title_full_unstemmed | Space Flight Enhances Stress Pathways in Human Neural Stem Cells |
| title_short | Space Flight Enhances Stress Pathways in Human Neural Stem Cells |
| title_sort | space flight enhances stress pathways in human neural stem cells |
| topic | microgravity space flight human neural stem cells cell stress intracranial hypertension |
| url | https://www.mdpi.com/2218-273X/14/1/65 |
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