Bibliographic record
Abstract
Myeloid cells reside in all normal tissues including normal arteries and their abundance is tightly regulated1,2. In the normal mouse aortic intima, myeloid cell numbers increase and reach a plateau at 16 to 20 weeks of age. Colony stimulating factor-1 (CSF1) is a key regulator of myeloid cell abundance, and mice deficient in CSF1 exhibit a profound reduction, in myeloid cells both in the artery intima and the adventitia. This thesis investigates the relevant source of CSF1 that regulate the abundance of myeloid cells in arteries. Experiments confirmed that the absolute numbers of intimal CD11c+ myeloid cells and adventitial CD68+ myeloid cells were reduced by >95% in CSF1-deficient (Csf1op/op) mice. Neutralizing antibodies to CSF1 or CSF1 receptor delivered for 1 week by a subcutaneously-implanted osmotic pump, reduced intimal and adventitial cells by 85% and 90%, respectively. Immunostaining revealed that CSF1 expression colocalized with luminal endothelial cells preferentially in the lesser curvature of the aortic arch, a region that harbors resident myeloid cells in the intima and is predisposed to atherosclerosis. Single cell mRNA sequencing of carefully isolated aortic intimal cells revealed preferential expression of CSF1 by endothelial cells while CSF1R is preferentially expressed by myeloid cells. Based on this observation, conditional endothelial-specific deletion of CSF1 in both Cdh5-CreERT2;CSF1flox/flox and BMX-Cre-ERT2;CSF1flox/flox mice revealed significantly reduced intimal, but not adventitial, myeloid cells. Circulating plasma levels of CSF1 were not changed in Cdh5-CreERT2;CSF1flox/flox mice, suggesting that endothelial cells are not the main source of soluble CSF1 in the plasma. Overall, our data demonstrate that CSF1/CSF1R signaling is required for the homeostatic maintenance of the intimal myeloid cells and that the production of CSF1 by adjacent arterial endothelial cells is critical. This defines an arterial intimal cell niche.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| 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 source (direct Gemma or distilled Codex), 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".