Beyond the GFAP-Astrocyte Protein Markers in the Brain

Abstract

The idea of central nervous system as one-man band favoring neurons is long gone. Now we all are aware that neurons and neuroglia are team players and constant communication between those various cell types is essential to maintain functional efficiency and a quick response to danger. Here, we summarize and discuss known and new markers of astroglial multiple functions, their natural heterogeneity, cellular interactions, aging and disease-induced dysfunctions. This review is focused on newly reported facts regarding astrocytes, which are beyond the old stereotypes. We present an up-to-date list of marker proteins used to identify a broad spectrum of astroglial phenotypes related to the various physiological and pathological nervous system conditions. The aim of this review is to help choose markers that are well-tailored for specific needs of further experimental studies, precisely recognizing differential glial phenotypes, or for diagnostic purposes. We hope it will help to categorize the functional and structural diversity of the astroglial population and ease a clear readout of future experimental results.

Cerebral Organoids Maintain the Expression of Neural Stem Cell-Associated Glycoepitopes and Extracellular Matrix

“…GFAP-expressing astrocytes were found at later stages, although large areas of the organoids were still free of GFAP signals ( Figure A3 ). GFAP is only one of several astrocyte markers and due to their heterogeneity, not all astrocytes express all markers [ 45 ]. Therefore, GFAP-negative astrocytes might be present in the organoids that were not labeled in our analysis.…”

Rapid Generation of Ventral Spinal Cord-like Astrocytes from Human iPSCs for Modeling Non-Cell Autonomous Mechanisms of Lower Motor Neuron Disease

“…Specifically, protoplasmic astrocytes are in close contact with synapses and actively regulate synapse formation, maturation and function. On the other hand, white matter fibrous astrocytes are involved in mechanisms underlying axonal Cells 2022, 11, 399 2 of 17 biology and myelination [9][10][11][12]. These functional diversities are correlated with defined molecular traits.…”

“…These functional diversities are correlated with defined molecular traits. For instance, protoplasmic and fibrous astrocytes differ in the expression level of the intermediate filament protein, glial fibrillary acidic protein (GFAP), which is significantly higher in fibrous astrocytes than in protoplasmic astrocytes [8][9][10][11][12].…”

Human iPSC-Derived Astrocytes: A Powerful Tool to Study Primary Astrocyte Dysfunction in the Pathogenesis of Rare Leukodystrophies

“…On the basis of their morphology, astrocytes were originally classified in two different populations: (i) protoplasmic astrocytes, highly branched astrocytes of the grey matter (GM), closely interacting with neuronal synapses and forming the “tripartite synapses”; and (ii) the fibrous astrocytes, a less branched cellular type, mostly present in the white matter (WM) where they contact oligodendrocytes and axons [ 3 , 4 ]. Evidence accumulated in the last 20 years have expanded this initial classification, revealing that astrocytes are a more heterogeneous group of cells showing regional specificities manifested by morphological, molecular and functional differences and whose knowledge is still to be completed [ 5 , 6 ]. By extending their processes and end-feet along blood vessels, perivascular astrocytes also take part to the formation of the blood-brain-barrier (BBB), the anatomic and biochemical barrier facilitating the entry of nutrients and excluding harmful substances into the brain [ 7 , 8 , 9 ].…”