Heterogeneity of white matter astrocytes in the human brain

Bugiani, Marianna; Plug, Bonnie C.; Man, Jodie H.K.; Breur, Marjolein; Knaap, Marjo S. van der

doi:10.1007/s00401-021-02391-3

Cited by 30 publications

(18 citation statements)

References 156 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Astrocytes also showed strong heterogeneity with WM tissue region: Clusters AS_5 and 6 were specific for BA4, clusters AS_4 and 7 were specific for CB and clusters AS_1, 2, 3, 9_ep, 11 and 12 were more abundant in CSC (Figure 4b,d) and so DEG analysis between regions reflected differences in these cluster marker genes such as increased ADGRV1 (AS_5) in BA4 (Figure 6a–c, Table S5). In addition, CSC astrocytes expressed more Glial Fibrillary Acidic Protein ( GFAP ) as previously reported in mouse 62 and more SKAP2 , similarly to oligodendroglia (Figure 6a,c, Table S5).This astrocyte regional specificity may relate to the known variation in astrocyte density in different WM tracts and may help understand regional variation in human astrocytopathies 63 . For example, mutations in the FAT3 gene are associated with Spinocere-bellar Ataxia (SCA) and this is more highly expressed in CB astrocytes, (Figure 6a, Table S5), with increasing expression with age (Figure 7d).…”

Section: Resultssupporting

confidence: 74%

“…In addition, CSC astrocytes expressed more Glial Fibrillary Acidic Protein (GFAP) as previously reported in mouse 62 and more SKAP2, similarly to oligodendroglia (Figure 6a,c, Table S5). This astrocyte regional specificity may relate to the known variation in astrocyte density in different WM tracts and may help understand regional variation in human astrocytopathies 63 . For example, mutations in the FAT3 gene are associated with Spinocerebellar Ataxia (SCA) and this is more highly expressed in CB astrocytes, (Figure 6a, Table S5), with increasing expression with age (Figure 7d).…”

Section: Regional Heterogeneity Is Marked In Wm Gliamentioning

confidence: 97%

See 1 more Smart Citation

Marked regional glial heterogeneity in the human white matter of the central nervous system

Seeker

Bestard-Cuche

Jäkel

et al. 2022

Preprint

View full text Add to dashboard Cite

The myelinated white matter tracts of the central nervous system (CNS) are essential for fast transmission of electrical impulses and are commonly affected in neurodegenerative diseases. However, these often uniquely human diseases differentially affect white matter regions, at various ages and between males and females, and we hypothesised that this is secondary to physiological variation in white matter glia with region, age and sex. Using single nucleus RNA sequencing of healthy human post-mortem samples, we find marked glial heterogeneity with tissue region (primary motor cortex, cerebellum, cervical spinal cord), with tissue-specific cell populations of oligodendrocyte precursor cells and astrocytes, and a spinal cord-enriched oligodendrocyte type that appears human-specific. Spinal cord microglia but not astrocytes show a more activated phenotype compared to brain. These regional effects, with additional differentially expressed genes with age and sex in all glial lineages, help explain pathological patterns of disease – essential knowledge for therapeutic strategies.

show abstract

Section: Resultssupporting

confidence: 74%

Section: Regional Heterogeneity Is Marked In Wm Gliamentioning

confidence: 97%

Marked regional glial heterogeneity in the human white matter of the central nervous system

Seeker

Bestard-Cuche

Jäkel

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Not only is the NVU is a complex structure by itself, but it is also heterogeneous throughout brain regions. Each component of the NVU itself has a unique transcriptome, proteome and epigenetic profile depending on the developmental origin and brain region where it is situated [32][33][34][35][36][37]. Another important aspect regarding the heterogeneity throughout the human brain is that the capillary density is higher in grey matter (GM) compared to white matter (WM).…”

Section: Introductionmentioning

confidence: 99%

The neurovascular unit in leukodystrophies: towards solving the puzzle

Zarekiani

Pinto

Hol

et al. 2022

Fluids Barriers CNS

Self Cite

View full text Add to dashboard Cite

The neurovascular unit (NVU) is a highly organized multicellular system localized in the brain, formed by neuronal, glial (astrocytes, oligodendrocytes, and microglia) and vascular (endothelial cells and pericytes) cells. The blood–brain barrier, a complex and dynamic endothelial cell barrier in the brain microvasculature that separates the blood from the brain parenchyma, is a component of the NVU. In a variety of neurological disorders, including Alzheimer’s disease, multiple sclerosis, and stroke, dysfunctions of the NVU occurs. There is, however, a lack of knowledge regarding the NVU function in leukodystrophies, which are rare monogenic disorders that primarily affect the white matter. Since leukodystrophies are rare diseases, human brain tissue availability is scarce and representative animal models that significantly recapitulate the disease are difficult to develop. The introduction of human induced pluripotent stem cells (hiPSC) now makes it possible to surpass these limitations while maintaining the ability to work in a biologically relevant human context and safeguarding the genetic background of the patient. This review aims to provide further insights into the NVU functioning in leukodystrophies, with a special focus on iPSC-derived models that can be used to dissect neurovascular pathophysiology in these diseases.

show abstract

“…Seeker et al dive into the heterogeneity of human oligodendroglia and the future challenges on how to push the field forward [6]. Bugiani et al describe the white matter astrocyte heterogeneity and discuss their role in towards development of astrogliopathies [2]. Schwabenland et al discuss current state of microglia heterogeneity and provide a practical guide for neuroscientist in general on how to analyze microglial phenotypes in depth in common neuropathologies [5].…”

mentioning

confidence: 99%

“…Bugiani et al . describe the white matter astrocyte heterogeneity and discuss their role in towards development of astrogliopathies [ 2 ]. Schwabenland et al .…”

mentioning

confidence: 99%