Human Neural Stem Cells Flown into Space Proliferate and Generate Young Neurons

Cepeda, Carlos; Vergnes, Laurent; Carpo, Nicholas; Schibler, Matthew J.; Bentolila, Laurent A.; Karouia, Fathi; Espinosa‐Jeffrey, Araceli

doi:10.3390/app9194042

Cited by 12 publications

(13 citation statements)

References 11 publications

(16 reference statements)

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“…Previously, we demonstrated that, just like in simulated microgravity, space microgravity (SPC-µG) induces enhanced proliferation of NSCs. We corroborated this during space flight [3] and confirmed that NSCs proliferated more than ground controls after space flight [4]. We also found that the vast majority of these cells adapted to Earth's gravity and displayed typical features of NSCs, such as self-renewal via normal proliferation, where cytokinesis occurred within the range of ground control cells without significant differences [4].…”

Section: Introductionsupporting

confidence: 75%

Space Flight Enhances Stress Pathways in Human Neural Stem Cells

Carpo,

Tran,

Biancotti

et al. 2024

Biomolecules

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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.

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Section: Introductionsupporting

confidence: 75%

Space Flight Enhances Stress Pathways in Human Neural Stem Cells

Carpo,

Tran,

Biancotti

et al. 2024

Biomolecules

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“…In addition, the cells revealed higher oxygen consumption and glycolysis compared with ground controls. These cells also kept their ability to become young neurons [53]. This was further corroborated in another study, which revealed that human neural stem cells proliferated seven times more in space in comparison to ground based controls [54].…”

Section: Gut Microbiome Angiogenesis and Link With Visual Impairmentsupporting

confidence: 60%

“…This study suggested that there may be weakening of the interior and exterior cellular structures of the retinal cells in a simulated microgravity environment, which might affect the function of the retinal layer. Nonetheless, it was recently reported that human neural stem cells proliferate when in space and express specific markers [53]. Neural stem cells are integral in the maintenance of the central nervous system's function.…”

Section: Gut Microbiome Angiogenesis and Link With Visual Impairmentmentioning

confidence: 99%

Effect of Microgravity Environment on Gut Microbiome and Angiogenesis

Siddiqui

Qaisar

Goswami

et al. 2021

Life

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Microgravity environments are known to cause a plethora of stressors to astronauts. Recently, it has become apparent that gut microbiome composition of astronauts is altered following space travel, and this is of significance given the important role of the gut microbiome in human health. Other changes observed in astronauts comprise reduced muscle strength and bone fragility, visual impairment, endothelial dysfunction, metabolic changes, behavior changes due to fatigue or stress and effects on mental well-being. However, the effects of microgravity on angiogenesis, as well as the connection with the gut microbiome are incompletely understood. Here, the potential association of angiogenesis with visual impairment, skeletal muscle and gut microbiome is proposed and explored. Furthermore, metabolites that are effectors of angiogenesis are deliberated upon along with their connection with gut bacterial metabolites. Targeting and modulating the gut microbiome may potentially have a profound influence on astronaut health, given its impact on overall human health, which is thus warranted given the likelihood of increased human activity in the solar system, and the determination to travel to Mars in future missions.

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“…We have previously reported that sim-µG increased the proliferation of rodent and human OLPs with the concomitant shortening of the cell cycle [ 18 ]. We have also reported that sim-µG enhances OLPs’ mitochondrial function and lipid metabolism [ 18 ] and that NSCs proliferate more while in space and after space flight [ 19 , 20 ]. These findings led us to hypothesize that space microgravity would produce similar results with regard to OLPs.…”

Section: Introductionmentioning

confidence: 99%

Delayed Maturation of Oligodendrocyte Progenitors by Microgravity: Implications for Multiple Sclerosis and Space Flight

Tran

Carpo

Shaka

et al. 2022

Life

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In previous studies, we examined the effects of space microgravity on human neural stem cells. To date, there are no studies on a different type of cell that is critical for myelination and electrical signals transmission, oligodendrocyte progenitors (OLPs). The purpose of the present study was to examine the behavior of space-flown OLPs (SPC-OLPs) as they were adapting to Earth’s gravity. We found that SPC-OLPs survived, and most of them proliferated normally. Nonetheless, some of them displayed incomplete cytokinesis. Both morphological and ontogenetic analyses showed that they remained healthy and expressed the immature OLP markers Sox2, PDGFR-α, and transferrin (Tf) after space flight, which confirmed that SPC-OLPs displayed a more immature phenotype than their ground control (GC) counterparts. In contrast, GC OLPs expressed markers that usually appear later (GPDH, O4, and ferritin), indicating a delay in SPC-OLPs’ development. These cells remained immature even after treatment with culture media designed to support oligodendrocyte (OL) maturation. The most remarkable and surprising finding was that the iron carrier glycoprotein Tf, previously described as an early marker for OLPs, was expressed ectopically in the nucleus of all SPC-OLPs. In contrast, their GC counterparts expressed it exclusively in the cytoplasm, as previously described. In addition, analysis of the secretome demonstrated that SPC-OLPs contained 3.5 times more Tf than that of GC cells, indicating that Tf is gravitationally regulated, opening two main fields of study to understand the upregulation of the Tf gene and secretion of the protein that keep OLPs at a progenitor stage rather than moving forward to more mature phenotypes. Alternatively, because Tf is an autocrine and paracrine factor in the central nervous system (CNS), in the absence of neurons, it accumulated in the secretome collected after space flight. We conclude that microgravity is becoming a novel platform to study why in some myelin disorders OLPs are present but do not mature.

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Human Neural Stem Cells Flown into Space Proliferate and Generate Young Neurons

Cited by 12 publications

References 11 publications

Space Flight Enhances Stress Pathways in Human Neural Stem Cells

Space Flight Enhances Stress Pathways in Human Neural Stem Cells

Effect of Microgravity Environment on Gut Microbiome and Angiogenesis

Delayed Maturation of Oligodendrocyte Progenitors by Microgravity: Implications for Multiple Sclerosis and Space Flight

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