Single-Cell Approaches Define the Murine Leptomeninges: Cortical Brain Interface as a Distinct Cellular Neighborhood Composed of Neural and Non-neural Cell Types
Bibliographic record
Abstract
The interface barrier between the brain surface and the adjacent meninges is important for regulating exchanges of fluid, protein, and immune cells between the CNS and periphery. However, the cell types that form this important interface are not yet fully defined. To address this limitation, we used single-cell RNA sequencing (scRNA-seq) and single-cell spatial transcriptomics together with morphological lineage tracing and immunostaining to describe the cell types forming the interface barrier of the adult murine cortex. We show that the cortical interface is composed of three major cell types, leptomeningeal cells, border astrocytes, and tissue-resident macrophages. On the nonparenchymal side, the interface is composed of transcriptionally distinct PDGFRα-positive leptomeningeal cells that are intermingled with macrophages. This leptomeningeal layer is lined by a population of transcriptionally distinct border astrocytes. The interface neighborhood is rich in growth factor mRNAs, including many leptomeningeal ligands predicted to act on both the border astrocytes and macrophages. On the CNS side of the interface is the relatively cell-sparse cortical layer 1 containing interneurons, microglia, parenchymal astrocytes, oligodendrocyte precursor cells, and oligodendrocytes. Except for the border astrocytes, layer 1 cells are not closely associated with the interface, suggesting that secreted ligands may be the major way the brain interface communicates with the underlying cortical parenchyma. Thus, our data provide a molecular/cellular resource describing the brain interface cell types and their interactions, thereby enabling future studies investigating how this distinct cellular compartment regulates CNS:periphery interactions.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".