Overcoming the inhibitory microenvironment surrounding oligodendrocyte progenitor cells following experimental demyelination

Darpan Saraswat, Hani J. Shayya, Jessie J. Polanco, Ajai Tripathi, R. Ross Welliver, Suyog U. Pol, Richard A. Seidman, Jacqueline E. Broome, Melanie A. O’Bara, Toin H. Kuppervelt, Joanna J. Phillips, Ranjan Dutta and Fraser J. Sim ()
Additional contact information
Darpan Saraswat: University at Buffalo
Hani J. Shayya: University at Buffalo
Jessie J. Polanco: University at Buffalo
Ajai Tripathi: Lerner Research Institute
R. Ross Welliver: University at Buffalo
Suyog U. Pol: University at Buffalo
Richard A. Seidman: University at Buffalo
Jacqueline E. Broome: University at Buffalo
Melanie A. O’Bara: University at Buffalo
Toin H. Kuppervelt: Radboud University Medical Center
Joanna J. Phillips: University of California
Ranjan Dutta: Lerner Research Institute
Fraser J. Sim: University at Buffalo

Nature Communications, 2021, vol. 12, issue 1, 1-18

Abstract: Abstract Chronic demyelination in the human CNS is characterized by an inhibitory microenvironment that impairs recruitment and differentiation of oligodendrocyte progenitor cells (OPCs) leading to failed remyelination and axonal atrophy. By network-based transcriptomics, we identified sulfatase 2 (Sulf2) mRNA in activated human primary OPCs. Sulf2, an extracellular endosulfatase, modulates the signaling microenvironment by editing the pattern of sulfation on heparan sulfate proteoglycans. We found that Sulf2 was increased in demyelinating lesions in multiple sclerosis and was actively secreted by human OPCs. In experimental demyelination, elevated OPC Sulf1/2 expression directly impaired progenitor recruitment and subsequent generation of oligodendrocytes thereby limiting remyelination. Sulf1/2 potentiates the inhibitory microenvironment by promoting BMP and WNT signaling in OPCs. Importantly, pharmacological sulfatase inhibition using PI-88 accelerated oligodendrocyte recruitment and remyelination by blocking OPC-expressed sulfatases. Our findings define an important inhibitory role of Sulf1/2 and highlight the potential for modulation of the heparanome in the treatment of chronic demyelinating disease.

Date: 2021
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-22263-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22263-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-22263-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().