Deciphering the Genetic Crosstalk between Microglia and Oligodendrocyte Precursor Cells during Demyelination and Remyelination Using Transcriptomic Data
Enrich-Bengoa, Jennifer (Universitat Autònoma de Barcelona. Institut de Neurociències)
Manich, Gemma (Universitat Autònoma de Barcelona. Departament de Ciències Morfològiques)
Degano, Irene R (Hospital del Mar (Barcelona, Catalunya))
Perálvarez-Marín, Alex (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Data:	2022
Resum:	Demyelinating disorders show impaired remyelination due to failure in the differentiation of oligodendrocyte progenitor cells (OPCs) into mature myelin-forming oligodendrocytes, a process driven by microglia-OPC crosstalk. Through conducting a transcriptomic analysis of microarray studies on the demyelination-remyelination cuprizone model and using human samples of multiple sclerosis (MS), we identified molecules involved in this crosstalk. Differentially expressed genes (DEGs) of specific regions/cell types were detected in GEO transcriptomic raw data after cuprizone treatment and in MS samples, followed by functional analysis with GO terms and WikiPathways. Additionally, microglia-OPC crosstalk between microglia ligands, OPC receptors and target genes was examined with the NicheNet model. We identified 108 and 166 DEGs in the demyelinated corpus callosum (CC) at 2 and 4 weeks of cuprizone treatment; 427 and 355 DEGs in the remyelinated (4 weeks of cuprizone treatment + 14 days of normal diet) compared to 2- and 4-week demyelinated CC; 252 DEGs in MS samples and 2730 and 12 DEGs in OPC and microglia of 4-week demyelinated CC. At this time point, we found 95 common DEGs in the CC and OPCs, and one common DEG in microglia and OPCs, mostly associated with myelin and lipid metabolism. Crosstalk analysis identified 47 microglia ligands, 43 OPC receptors and 115 OPC target genes, all differentially expressed in cuprizone-treated samples and associated with myelination. Our differential expression pipeline identified demyelination/remyelination transcriptomic biomarkers in studies using diverse platforms and cell types/tissues. Cellular crosstalk analysis yielded novel markers of microglia ligands, OPC receptors and target genes.
Ajuts:	Agencia Estatal de Investigación BFU2017-87843-R Agencia Estatal de Investigación PID2020-120222GB-I00 Ministerio de Economía y Competitividad CB16/11/00229 Instituto de Salud Carlos III PI21/00163
Nota:	Altres ajuts: Fundació La Marató de TV3 (202119-33)
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Corpus callosum ; Cuprizone ; Demyelination ; Oligodendrocytes ; Microglia
Publicat a:	International journal of molecular sciences, Vol. 23 Núm. 23 (november 2022) , p. 14868, ISSN 1422-0067

DOI: 10.3390/ijms232314868
PMID: 36499195

17 p, 3.6 MB

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