Hypoxic Preconditioned Neural Stem Cell-Derived Extracellular Vesicles Contain Distinct Protein Cargo from Their Normal Counterparts
Abstract
:1. Introduction
2. Results
2.1. NSCs Characterization, Identification, and Differentiation
2.2. Hypoxic Preconditioning Affects NSC Viability
2.3. Characterization of Normal vs. Hypoxic Preconditioned NSC-Derived EVs
2.4. Proteomic Profiling of Normal vs. Hypoxic Preconditioned NSC-Derived EVs
2.5. Differentially Expressed Proteins Enriched in Specific Biological Pathways
2.6. Detection of Elevated mRNA Transcripts of Upregulated Proteins within HP-EVs
3. Discussion
4. Methods and Materials
4.1. Primary NSC Isolation, Culture, and Passaging
4.2. Immunohistochemistry
4.3. Hypoxic Preconditioning
4.4. NSC Proliferation and Cell Viability Assay
4.5. Extracellular Vesicle Isolation
4.6. Characterization of EVs
4.7. Western Blotting
4.8. EV Analysis with ExoView
4.9. Extracellular Vesicle Proteome Profiling
4.10. EV RNA Isolation
4.11. RT-qPCR
4.12. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Gene Name | Up/Down-Regulated | Description | p-Value | FC |
---|---|---|---|---|
Ints4 | Up | Integrator complex subunit 4 | 0.01973179 | 4.61333333 |
Rpl18 | Up | 60S ribosomal protein L18 | 0.03111818 | 2.18979266 |
Moxd1 | Up | DBH-like monooxygenase protein 1 | 0.03943133 | 1.96772997 |
Rpl7 | Up | 60S ribosomal protein L7 | 0.0180495 | 1.9379361 |
Cadm2 | Up | Cell adhesion molecule 2 | 0.04979333 | 1.76720858 |
Rps8 | Up | 40S ribosomal protein S8 | 0.0437712 | 1.69393939 |
Tubb5 | Up | Tubulin beta-5 chain | 0.04878117 | 1.65571049 |
Rpl34 | Up | 60S ribosomal protein L34 | 0.04677985 | 1.64879179 |
Bhmt | Up | Betaine--homocysteine S-methyltransferase 1 | 0.04297693 | 1.63417847 |
Cyfip1 | Up | Cytoplasmic FMR1-interacting protein 1 | 0.04924497 | 1.60110533 |
Rpl7a | Up | 60S ribosomal protein L7a | 0.03507391 | 1.5979214 |
Up | Uncharacterized protein C2orf72 | 0.0137668 | 1.45398773 | |
Ctnna1 | Up | Catenin alpha-1 | 0.0172758 | 1.41868198 |
Cdc42 | Up | Cell division control protein 42 | 0.02439533 | 1.41036457 |
Adam9 | Up | Disintegrin and metalloproteinase domain-containing protein 9 | 0.02993997 | 1.3840882 |
Atp2b1 | Up | Plasma membrane calcium-transporting ATPase 1 | 0.03146976 | 1.37318303 |
Slc6a1 | Up | Sodium- and chloride-dependent GABA transporter 1 | 0.00137502 | 1.34094235 |
Cnp | Up | 2′,3′-cyclic-nucleotide 3′-phosphodiesterase | 0.01201357 | 1.28534704 |
Nkain3 | Up | Sodium/potassium-transporting ATPase subunit beta-1-interacting protein 3 | 0.03002822 | 1.2425007 |
Cask | Up | Peripheral plasma membrane protein CASK | 0.02686701 | 1.23588597 |
Actr3 | Down | Actin-related protein 3 | 0.03585085 | 0.82959744 |
Npc2 | Down | NPC intracellular cholesterol transporter 2 | 0.03261727 | 0.80202703 |
Blmh | Down | Bleomycin hydrolase | 0.04554183 | 0.79856115 |
Psph | Down | Phosphoserine phosphatase | 0.01691792 | 0.79636282 |
Atp6v1a | Down | V-type proton ATPase catalytic subunit A | 0.01888445 | 0.78930888 |
Mapre1 | Down | Microtubule-associated protein RP/EB family member 1 | 0.04938624 | 0.77795066 |
Elavl1 | Down | ELAV-like protein 1 | 0.0289941 | 0.7691287 |
Glo1 | Down | Lactoylglutathione lyase | 0.04542562 | 0.76422585 |
Atp6v1c1 | Down | V-type proton ATPase subunit C 1 | 0.03806311 | 0.73310225 |
Plbd2 | Down | Putative phospholipase B-like 2 | 0.00952826 | 0.73010381 |
Ddah1 | Down | N(G),N(G)-dimethylarginine dimethylaminohydrolase 1 | 0.01486318 | 0.72043011 |
Hsp90aa1 | Down | Heat shock protein HSP 90-alpha | 0.0227131 | 0.70524297 |
Psmb2 | Down | Proteasome subunit beta type-2 | 0.04881743 | 0.6939856 |
Ndufa4 | Down | Cytochrome c oxidase subunit NDUFA4 | 0.03014898 | 0.65645061 |
Dctn1 | Down | Dynactin subunit 1 | 0.02291716 | 0.65439504 |
Oat | Down | Ornithine aminotransferase | 0.02557392 | 0.6400164 |
Rpn2 | Down | Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit 2 | 0.0427866 | 0.63445035 |
Ak3 | Down | GTP:AMP phosphotransferase AK3 | 0.04882486 | 0.63211589 |
Psap | Down | Prosaposin | 0.02450609 | 0.62423873 |
Hnrnpab | Down | Heterogeneous nuclear ribonucleoprotein A/B | 0.03999623 | 0.61628612 |
Pdia3 | Down | Protein disulfide-isomerase A3 | 0.0477473 | 0.57666535 |
Actg2 | Down | Actin, gamma-enteric smooth muscle | 0.01623375 | 0.50677966 |
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Gharbi, T.; Liu, C.; Khan, H.; Zhang, Z.; Yang, G.-Y.; Tang, Y. Hypoxic Preconditioned Neural Stem Cell-Derived Extracellular Vesicles Contain Distinct Protein Cargo from Their Normal Counterparts. Curr. Issues Mol. Biol. 2023, 45, 1982-1997. https://doi.org/10.3390/cimb45030127
Gharbi T, Liu C, Khan H, Zhang Z, Yang G-Y, Tang Y. Hypoxic Preconditioned Neural Stem Cell-Derived Extracellular Vesicles Contain Distinct Protein Cargo from Their Normal Counterparts. Current Issues in Molecular Biology. 2023; 45(3):1982-1997. https://doi.org/10.3390/cimb45030127
Chicago/Turabian StyleGharbi, Tahereh, Chang Liu, Haroon Khan, Zhijun Zhang, Guo-Yuan Yang, and Yaohui Tang. 2023. "Hypoxic Preconditioned Neural Stem Cell-Derived Extracellular Vesicles Contain Distinct Protein Cargo from Their Normal Counterparts" Current Issues in Molecular Biology 45, no. 3: 1982-1997. https://doi.org/10.3390/cimb45030127