The Matrix Receptor CD44 Is Present in Astrocytes Throughout the Human CNS and Accumulates in Hypoxia and Seizures

Abstract

In the mammalian isocortex CD44, a cell surface receptor for extracellular matrix molecules, is present in pial-based and fibrous astrocytes of white matter, but not the protoplasmic astrocytes. In the hominid isocortex, CD44+ astrocytes comprise the subpial “interlaminar” astrocytes, sending long processes into the cortex. The hippocampus also contains similar astrocytes. We have examined all levels of the human CNS and found CD44+ astrocytes in every region. Astrocytes in white matter and astrocytes that interact with large blood vessels, but not capillaries in gray matter, are CD44+, the latter extending long processes into the parenchyma. Motor neurons in the brainstem and spinal cord, such as oculomotor, facial, hypoglossal, and in the anterior horn of the spinal cord, are surrounded by CD44+ processes, contrasting with neurons in the cortex, basal ganglia and thalamus. We found CD44+ processes that intercalate between ependymal cells to reach the ventricle and that show a location-specific presence. We also found a CD44+ astrocyte in the molecular layer of the cerebellar cortex. Protoplasmic astrocytes, which do not normally contain CD44, acquire it in pathologies like hypoxia and seizures.

Glioblastoma is spatially organized by neurodevelopmental programs and a glial-like wound healing response

“…This association was observed across different tumors, where TNC expression correlated with areas of GW-like states and decreased proliferation (Figure S7B). We observed the expression of other notable genes such as CD44 and GAP43 along our latent time axis (Figure 6E); both of these genes, together with TNC, have been previously associated with MES1 Neftel subtype, but are also expressed by astrocytes and reactive astrocytes [57][58][59] . We observed a layered structured defined by GAP43, CD44, TNC, and VEGFA, where TNC region corresponded to the layer found between CD44/GAP43 and VEGFA (highest hypoxia) (Figure 6I-III.b).…”

The spatial landscape of glial pathology and T-cell response in Parkinson’s disease substantia nigra

“…Astrocytes play roles in PD 99 . We and others have shown that astrocytes can be distinguished by CD44 expression into fibrous-like and protoplasmic 100 . We assigned astrocytic nuclei to a protoplasmic or fibrous-like sublineage and conducted DGE analysis ( Fig.…”

“…We then examined evidence for a transition from protoplasmic to fibrous-like states in PD, as we have seen in HD, hypoxia, and seizures 36,100 , using pseudotime analysis which is a means to order cells along a trajectory of gene signature. We ordered cells on the axis of variation along the genes that differ between the two astrocyte sublineages ( Fig.…”

CNS/PNS proteoglycans functionalize neuronal and astrocyte niche microenvironments optimizing cellular activity by preserving membrane polarization dynamics, ionic microenvironments, ion fluxes, neuronal activation, and network neurotransductive capacity

“…It is important that such structures be maintained, dysfunctional PNNs are associated with neurodegenerative disorders (Li et al., 2024; Li, Li, et al., 2023). CD44 is also widely expressed by astrocytes throughout the CNS (Al‐Dalahmah et al., 2024) and its expression levels are elevated in hypoxic conditions and in migratory cells in glioblastoma (Inoue et al., 2023). CD44 is a multifunctional molecule that promotes the invasion and proliferation of tumor cells via a number of signaling pathways.…”