# The Effects of Microgravity on Differentiation and Regeneration in Neural Stem Cells

**Authors:** Qiuyan Hao, Hao Tian, Na Lv, Fengtang Yang, Hui Zhen, Zhonghong Cao

PMC · DOI: 10.3390/cells15040371 · 2026-02-20

## TL;DR

This paper reviews how microgravity affects neural stem cells, showing both promoting and inhibiting effects on their growth and regeneration.

## Contribution

It synthesizes conflicting findings on microgravity's impact on NSCs and explores underlying mechanisms for space and regenerative medicine.

## Key findings

- Real spaceflight increases NSC proliferation but reduces neurosphere volume.
- RWV systems promote neuron and astrocyte generation, while RCCSs inhibit differentiation.
- Phenotypic outcomes depend on experimental conditions, cell sources, and observation time.

## Abstract

What are the main findings?
In scientific research, perspectives diverge on microgravity’s impact on neural stem cell (NSC) development, with some studies indicating promotion and others inhibition.This review clarifies the key features of NSCs, examines the contrasting effects of microgravity on their development and regeneration (both promoting and inhibiting), and explores the underlying molecular and cellular mechanisms. These insights offer valuable guidance for NSC-based therapies in space and regenerative medicine.

In scientific research, perspectives diverge on microgravity’s impact on neural stem cell (NSC) development, with some studies indicating promotion and others inhibition.

This review clarifies the key features of NSCs, examines the contrasting effects of microgravity on their development and regeneration (both promoting and inhibiting), and explores the underlying molecular and cellular mechanisms. These insights offer valuable guidance for NSC-based therapies in space and regenerative medicine.

What are the implications of the main findings?
These findings are expected to inspire novel approaches for studying neural systems pertinent to space medicine while facilitating the optimization of NSC applications in regenerative medicine.

These findings are expected to inspire novel approaches for studying neural systems pertinent to space medicine while facilitating the optimization of NSC applications in regenerative medicine.

Neural stem cells (NSCs) are self-renewing, multipotent cells of the central nervous system (CNS) that can differentiate into a range of specialized cell types, including neurons, astrocytes, and oligodendrocytes (OLs). Due to their remarkable ability to self-renew and differentiate, NSCs hold immense potential for the treatment of neurodegenerative diseases (NDDs). However, clinical translation remains hindered by challenges such as expansion difficulties and phenotypic drift. This review synthesizes evidence on the divergent effects of microgravity on NSC biology. While real spaceflight has been shown to enhance NSC proliferation, it paradoxically reduces neurosphere volume. Microgravity simulations yield contrasting results: rotating wall vessel (RWV) systems promote neuron and astrocyte generation, whereas rotating cell culture systems (RCCSs) inhibit differentiation despite the use of pro-differentiation media. These phenotypic variations critically depend on experimental conditions, cell sources, and observation time. Future research should focus on elucidating cross-pathway interactions and optimizing culture parameters to enable clinical-scale NSC applications.

## Full-text entities

- **Genes:** Sox2 (SRY-box transcription factor 2) [NCBI Gene 499593] {aka RGD1565646}, Rbfox3 (RNA binding fox-1 homolog 3) [NCBI Gene 287847] {aka Hrnbp3, Neun, RGD1560070}, App (amyloid beta precursor protein) [NCBI Gene 11820] {aka Abeta, Abpp, Adap, Ag, Cvap, E030013M08Rik}, Bdnf (brain derived neurotrophic factor) [NCBI Gene 12064], MIAT (myocardial infarction associated transcript) [NCBI Gene 440823] {aka C22orf35, GOMAFU, LINC00066, NCRNA00066, RNCR2, lncRNA-MIAT}, Cdk1 (cyclin dependent kinase 1) [NCBI Gene 12534] {aka Cdc2, Cdc2a, p34<CDC2>}, Ngf (nerve growth factor) [NCBI Gene 18049] {aka Ngfb, beta-NGF}, YAP1 (Yes1 associated transcriptional regulator) [NCBI Gene 10413] {aka COB1, YAP, YAP-1, YAP2, YAP65, YKI}, Psen1 (presenilin 1) [NCBI Gene 19164] {aka Ad3h, PS-1, PS1, S182}, Notch1 (notch receptor 1) [NCBI Gene 25496] {aka NOTCH, TAN1}, GADD45G (growth arrest and DNA damage inducible gamma) [NCBI Gene 10912] {aka CR6, DDIT2, GADD45gamma, GRP17}, Mapk8 (mitogen-activated protein kinase 8) [NCBI Gene 26419] {aka JNK, JNK1, Prkm8, SAPK1}, Gfap (glial fibrillary acidic protein) [NCBI Gene 24387], Klf4 (KLF transcription factor 4) [NCBI Gene 114505] {aka GKLF}, STK4 (serine/threonine kinase 4) [NCBI Gene 6789] {aka KRS2, MST1, YSK3}, ASCL1 (achaete-scute family bHLH transcription factor 1) [NCBI Gene 429] {aka ASH1, HASH1, MASH1, bHLHa46}, NEUROG1 (neurogenin 1) [NCBI Gene 4762] {aka AKA, CCDDRD, Math4C, NEUROD3, bHLHa6, ngn1}, Pax6 (paired box 6) [NCBI Gene 25509], KLF4 (KLF transcription factor 4) [NCBI Gene 9314] {aka EZF, GKLF}, REST (RE1 silencing transcription factor) [NCBI Gene 5978] {aka DFNA27, GINGF5, HGF5, NRSF, WT6, XBR}, HES1 (hes family bHLH transcription factor 1) [NCBI Gene 3280] {aka HES-1, HHL, HRY, bHLHb39}, BMP1 (bone morphogenetic protein 1) [NCBI Gene 649] {aka OI13, PCOLC, PCP, TLD}, Cdk1 (cyclin-dependent kinase 1) [NCBI Gene 54237] {aka Cdc2, Cdc2a}, Cntf (ciliary neurotrophic factor) [NCBI Gene 12803], RBM3 (RNA binding motif protein 3) [NCBI Gene 5935] {aka IS1-RNPL, RNPL}, Wnt5a (wingless-type MMTV integration site family, member 5A) [NCBI Gene 22418] {aka 8030457G12Rik, Wnt-5a}, Ntf3 (neurotrophin 3) [NCBI Gene 81737], Wnt3 (wingless-type MMTV integration site family, member 3) [NCBI Gene 22415] {aka Int-4, Wnt-3}, RBPJ (recombination signal binding protein for immunoglobulin kappa J region) [NCBI Gene 3516] {aka AOS3, CBF-1, CBF1, IGKJRB, IGKJRB1, KBF2}, MAP2 (microtubule associated protein 2) [NCBI Gene 4133] {aka MAP-2, MAP2A, MAP2B, MAP2C}, Ctnnb1 (catenin beta 1) [NCBI Gene 12387] {aka Bfc, Catnb, Mesc}, KLF13 (KLF transcription factor 13) [NCBI Gene 51621] {aka BTEB3, FKLF2, NSLP1, RFLAT-1, RFLAT1}, Sox2 (SRY (sex determining region Y)-box 2) [NCBI Gene 20674] {aka Sox-2, lcc, ysb}, Mki67 (antigen identified by monoclonal antibody Ki 67) [NCBI Gene 17345] {aka D630048A14Rik, Ki-67, Ki67}, Wnt7a (wingless-type MMTV integration site family, member 7A) [NCBI Gene 22421] {aka Wnt-7a, px, tw}, Il10 (interleukin 10) [NCBI Gene 16153] {aka CSIF, If2a, Il-10}, Map2 (microtubule-associated protein 2) [NCBI Gene 25595] {aka MAP2R, Mtap2}, CREB1 (cAMP responsive element binding protein 1) [NCBI Gene 1385] {aka CREB, CREB-1}, KLF6 (KLF transcription factor 6) [NCBI Gene 1316] {aka BCD1, CBA1, COPEB, CPBP, GBF, PAC1}, HES5 (hes family bHLH transcription factor 5) [NCBI Gene 388585] {aka bHLHb38}, GFAP (glial fibrillary acidic protein) [NCBI Gene 2670] {aka ALXDRD}
- **Diseases:** neurological diseases (MESH:D020271), spinal cord injuries (MESH:D013119), Neurological disorders (MESH:D009461), PD (MESH:D010300), injury to (MESH:D014947), NDDs (MESH:D019636), CNS diseases (MESH:D002493), ICD (OMIM:252500), HD (MESH:D006816), AD (MESH:D000544), nervous system diseases (MESH:D009422), cognitive deficits (MESH:D003072), nerve injury (MESH:D000080902), tumorigenic (MESH:D002471), ALS (MESH:D000690), cardiovascular disease (MESH:D002318)
- **Chemicals:** cAMP (MESH:D000242), oxygen (MESH:D010100), ATP (MESH:D000255), RCCS (-), VPA (MESH:D014635)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Caenorhabditis elegans (species) [taxon 6239], Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116]

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12939388/full.md

---
Source: https://tomesphere.com/paper/PMC12939388