Cell-type-specific mechanistic drivers of progressive multiple sclerosis lesions
Аутори
ML, ElkjaerA, Hartebrodt
M, Oubounyt
A, Weber
L, Vitved
R, Reynolds
M, Thomassen
R, Rottger
J, Baumbach
Z, Illes
Остала ауторства
Morić, IvanaĐorđević, Valentina
Конференцијски прилог (Објављена верзија)
,
© 2023 Institute of Molecular Genetics and Genetic Engineering, University of Belgrade
Метаподаци
Приказ свих података о документуАпстракт
Understanding the drivers of compartmentalized and sustained inflammation in the
brain of progressive multiple sclerosis (PMS) remains elusive. To investigate the interplay
between inter- and intra-cellular molecular mechanisms in white matter (WM) lesions, we
integrated single-cell transcriptome and chromatin accessibility data from PMS lesions
with spatial transcriptomics of chronic active lesion borders. We identified a PMS-specific
oligodendrocyte genetic program governed by the Krüppel-like factor and specificity
protein (KLF/SP) gene family, implicated in myelination and stress-induced iron uptake.
Additionally, we found high expression of transferrin gene (TF) and its receptor megalin
(LRP2) across lesion types, suggesting autocrine communication of iron uptake potential
related to iron rim lesion in smoldering MS. Additionally, inflammatory phenotype of
oligodendrocytes expressing osteopontin gene and complement were observed at
chronic active lesion edges. Inside th...e chronic active lesion, the axonal damage biomarker,
neurofilament light (NFL) gene expression was upregulated, and an astrocytic-neuronal
axis through fibroblast growth factor (FGF) signaling (FGFR3-FGF13) was present.
Additionally, a metabolic astrocyte phenotype at the lesion border potentially segregates
inflammation areas. We also identified two distinct B cell co-expression networks with
different locations and gene expressions, preferring different lesion types. Overall, singlecell
multi-omics enabled the identification of specific cell types with unique molecular
profiles, cell-cell communications, and spatial context, contributing to lesion fate.
Кључне речи:
white matter lesions / single-cell multi-omics / progressive multiple sclerosis / spatial transcriptomics / iron metabolism / FGF signaling / chronic active lesionИзвор:
4th Belgrade Bioinformatics Conference, 2023, 4, 47-47Издавач:
- Belgrade : Institute of molecular genetics and genetic engineering
Напомена:
- Book of abstract: 4th Belgrade Bioinformatics Conference, June 19-23, 2023
Колекције
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - CONF AU - ML, Elkjaer AU - A, Hartebrodt AU - M, Oubounyt AU - A, Weber AU - L, Vitved AU - R, Reynolds AU - M, Thomassen AU - R, Rottger AU - J, Baumbach AU - Z, Illes PY - 2023 UR - https://belbi.bg.ac.rs/ UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1989 AB - Understanding the drivers of compartmentalized and sustained inflammation in the brain of progressive multiple sclerosis (PMS) remains elusive. To investigate the interplay between inter- and intra-cellular molecular mechanisms in white matter (WM) lesions, we integrated single-cell transcriptome and chromatin accessibility data from PMS lesions with spatial transcriptomics of chronic active lesion borders. We identified a PMS-specific oligodendrocyte genetic program governed by the Krüppel-like factor and specificity protein (KLF/SP) gene family, implicated in myelination and stress-induced iron uptake. Additionally, we found high expression of transferrin gene (TF) and its receptor megalin (LRP2) across lesion types, suggesting autocrine communication of iron uptake potential related to iron rim lesion in smoldering MS. Additionally, inflammatory phenotype of oligodendrocytes expressing osteopontin gene and complement were observed at chronic active lesion edges. Inside the chronic active lesion, the axonal damage biomarker, neurofilament light (NFL) gene expression was upregulated, and an astrocytic-neuronal axis through fibroblast growth factor (FGF) signaling (FGFR3-FGF13) was present. Additionally, a metabolic astrocyte phenotype at the lesion border potentially segregates inflammation areas. We also identified two distinct B cell co-expression networks with different locations and gene expressions, preferring different lesion types. Overall, singlecell multi-omics enabled the identification of specific cell types with unique molecular profiles, cell-cell communications, and spatial context, contributing to lesion fate. PB - Belgrade : Institute of molecular genetics and genetic engineering C3 - 4th Belgrade Bioinformatics Conference T1 - Cell-type-specific mechanistic drivers of progressive multiple sclerosis lesions EP - 47 SP - 47 VL - 4 UR - https://hdl.handle.net/21.15107/rcub_imagine_1989 ER -
@conference{ author = "ML, Elkjaer and A, Hartebrodt and M, Oubounyt and A, Weber and L, Vitved and R, Reynolds and M, Thomassen and R, Rottger and J, Baumbach and Z, Illes", year = "2023", abstract = "Understanding the drivers of compartmentalized and sustained inflammation in the brain of progressive multiple sclerosis (PMS) remains elusive. To investigate the interplay between inter- and intra-cellular molecular mechanisms in white matter (WM) lesions, we integrated single-cell transcriptome and chromatin accessibility data from PMS lesions with spatial transcriptomics of chronic active lesion borders. We identified a PMS-specific oligodendrocyte genetic program governed by the Krüppel-like factor and specificity protein (KLF/SP) gene family, implicated in myelination and stress-induced iron uptake. Additionally, we found high expression of transferrin gene (TF) and its receptor megalin (LRP2) across lesion types, suggesting autocrine communication of iron uptake potential related to iron rim lesion in smoldering MS. Additionally, inflammatory phenotype of oligodendrocytes expressing osteopontin gene and complement were observed at chronic active lesion edges. Inside the chronic active lesion, the axonal damage biomarker, neurofilament light (NFL) gene expression was upregulated, and an astrocytic-neuronal axis through fibroblast growth factor (FGF) signaling (FGFR3-FGF13) was present. Additionally, a metabolic astrocyte phenotype at the lesion border potentially segregates inflammation areas. We also identified two distinct B cell co-expression networks with different locations and gene expressions, preferring different lesion types. Overall, singlecell multi-omics enabled the identification of specific cell types with unique molecular profiles, cell-cell communications, and spatial context, contributing to lesion fate.", publisher = "Belgrade : Institute of molecular genetics and genetic engineering", journal = "4th Belgrade Bioinformatics Conference", title = "Cell-type-specific mechanistic drivers of progressive multiple sclerosis lesions", pages = "47-47", volume = "4", url = "https://hdl.handle.net/21.15107/rcub_imagine_1989" }
ML, E., A, H., M, O., A, W., L, V., R, R., M, T., R, R., J, B.,& Z, I.. (2023). Cell-type-specific mechanistic drivers of progressive multiple sclerosis lesions. in 4th Belgrade Bioinformatics Conference Belgrade : Institute of molecular genetics and genetic engineering., 4, 47-47. https://hdl.handle.net/21.15107/rcub_imagine_1989
ML E, A H, M O, A W, L V, R R, M T, R R, J B, Z I. Cell-type-specific mechanistic drivers of progressive multiple sclerosis lesions. in 4th Belgrade Bioinformatics Conference. 2023;4:47-47. https://hdl.handle.net/21.15107/rcub_imagine_1989 .
ML, Elkjaer, A, Hartebrodt, M, Oubounyt, A, Weber, L, Vitved, R, Reynolds, M, Thomassen, R, Rottger, J, Baumbach, Z, Illes, "Cell-type-specific mechanistic drivers of progressive multiple sclerosis lesions" in 4th Belgrade Bioinformatics Conference, 4 (2023):47-47, https://hdl.handle.net/21.15107/rcub_imagine_1989 .