CpG methylation changes in human mesenchymal and neural stem cells in response to in vitro niche modifications

Martina Gyimesi; Lotta E Oikari; Chieh Yu; Heidi G Sutherland; Dale R Nyholt; Lyn R Griffiths; Andre J Van Wijnen; Rachel K Okolicsanyi; Larisa M Haupt

doi:10.1016/j.biochi.2024.04.007

CpG methylation changes in human mesenchymal and neural stem cells in response to in vitro niche modifications

Biochimie. 2024 Apr 17:S0300-9084(24)00082-8. doi: 10.1016/j.biochi.2024.04.007. Online ahead of print.

Authors

Martina Gyimesi¹, Lotta E Oikari¹, Chieh Yu¹, Heidi G Sutherland¹, Dale R Nyholt², Lyn R Griffiths¹, Andre J Van Wijnen³, Rachel K Okolicsanyi⁴, Larisa M Haupt⁵

Affiliations

¹ Stem Cell and Neurogenesis Group, Genomics Research Centre, Centre for Genomics and Personalised Health, School of Biomedical Sciences, Queensland University of Technology, Australia.
² Statistical and Genomic Epidemiology Laboratory, School of Biomedical Sciences, Faculty of Health and Centre for Genomics and Personalised Health, Queensland University of Technology, Brisbane, QLD, Australia.
³ Department of Biochemistry, University of Vermont, Australia.
⁴ Stem Cell and Neurogenesis Group, Genomics Research Centre, Centre for Genomics and Personalised Health, School of Biomedical Sciences, Queensland University of Technology, Australia; Max Planck Queensland Centre for the Materials Science of Extracellular Matrices, Australia.
⁵ Stem Cell and Neurogenesis Group, Genomics Research Centre, Centre for Genomics and Personalised Health, School of Biomedical Sciences, Queensland University of Technology, Australia; ARC Training Centre for Cell and Tissue Engineering Technologies, Queensland University of Technology (QUT), Australia; Max Planck Queensland Centre for the Materials Science of Extracellular Matrices, Australia; Centre for Biomedical Technologies, Queensland University of Technology (QUT), 60 Musk Ave., Kelvin Grove, QLD 4059, Australia. Electronic address: larisa.haupt@qut.edu.au.

PMID: 38640996
DOI: 10.1016/j.biochi.2024.04.007

Abstract

Stem cell therapies hold promise in addressing the burden of neurodegenerative diseases with human embryonic neural stem cells (hNSC-H9s) and bone marrow-derived human mesenchymal stem cells (hMSCs) as viable candidates. The induction of hMSC neurospheres (hMSC-IN) generate a more lineage-restricted common neural progenitor-like cell population, potentially tunable by heparan sulfate proteoglycans (HSPGs). We examined CpG (5 mC) site methylation patterns using Illumina Infinium 850 K EPIC arrays in hNSC-H9, hMSCs and hMSC-IN cultures with HSPG agonist heparin at early and late phases of growth. We identified key regulatory CpG sites in syndecans (SDC2; SDC4) that potentially regulate gene expression in monolayers. Unique hMSC-IN hypomethylation in glypicans (GPC3; GPC4) underscore their significance in neural lineages with Sulfatase 1 and 2 (SULF1 &2) CpG methylation changes potentially driving the neurogenic shift. hMSC-INs methylation levels at SULF1 CpG sites and SULF2:cg25401628 were more closely aligned with hNSC-H9 cells than with hMSCs. We further suggest SOX2 regulation governed by lncSOX2-Overall Transcript (lncSOX2-OT) methylation changes with preferential activation of ENO2 over other neuronal markers within hMSC-INs. Our findings illuminate epigenetic dynamics governing neural lineage commitment of hMSC-INs offering insights for targeted mechanisms for regenerative medicine and therapeutic strategies.

Keywords: Adult human stem cells; CpG methylation; Heparan sulfate proteoglycans; Induced neurosphere; Neurogenesis.