Glial progenitor cells of the adult human white and grey matter are contextually distinct

• Published in: Glia 2023-03, Vol.71 (3), p.524-540
• Main Authors: Osorio, Maria Joana, Mariani, John N., Zou, Lisa, Schanz, Steven J., Heffernan, Kate, Cornwell, Adam, Goldman, Steven A.
• Format: Article
• Language: English
• Subjects: Adult; Animals; Astrocytes - metabolism; Brain - metabolism; Cells (biology); Cerebral cortex; Complexity; Cytoskeleton; Eye Proteins - metabolism; Gene expression; Genes; Genomic analysis; glial heterogeneity; Glial stem cells; Gray Matter - metabolism; Heterogeneity; human glial progenitor cells; Humans; Membrane Proteins - metabolism; Mice; Morphology; Neocortex; Nerve Tissue Proteins - metabolism; Neuroglia - metabolism; NG2; Progenitor cells; Selectivity; Stem Cells - metabolism; Substantia alba; Substantia grisea; white and grey matter; White Matter - metabolism; Wnt protein
• ISSN: 0894-1491; 1098-1136
• DOI: 10.1002/glia.24291

Genomic analyses have revealed heterogeneity among glial progenitor cells (GPCs), but the compartment selectivity of human GPCs (hGPCs) is unclear. Here, we asked if GPCs of human grey and white brain matter are distinct in their architecture and associated gene expression. RNA profiling of NG2‐defined hGPCs derived from adult human neocortex and white matter differed in their expression of genes involved in Wnt, NOTCH, BMP and TGFβ signaling, suggesting compartment‐selective biases in fate and self‐renewal. White matter hGPCs over‐expressed the BMP antagonists BAMBI and CHRDL1, suggesting their tonic suppression of astrocytic fate relative to cortical hGPCs, whose relative enrichment of cytoskeletal genes presaged their greater morphological complexity. In human glial chimeric mice, cortical hGPCs assumed larger and more complex morphologies than white matter hGPCs, and both were more complex than their mouse counterparts. These findings suggest that human grey and white matter GPCs comprise context‐specific pools with distinct functional biases. Main Points GPCs in the adult human white and gray matter are transcriptionally distinct. GM and WM hGPCs differentially express WNT, NOTCH, BMP and TGFβ pathway genes. The expression of BMP antagonists is significantly higher in WM hGPCs. hGPCs in the GM are larger and more complex than in the WM.