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Single-cell analysis reveals fibroblast heterogeneity and myeloid-derived adipocyte progenitors in murine skin wounds

2019· article· en· 542 citations· W2911253006 on OpenAlex· 10.1038/s41467-018-08247-x

Why is this work in the frame?

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

Canadian funderA Canadian agency funded it. The work may carry no Canadian affiliation at all.

No Canadian affiliation. An affiliation-only frame — the usual design — would never have seen this work. It is one of the works that make the case for inverting the frame.

Machine scores (provisional)

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

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.

Opus teacher head0.021
GPT teacher head0.304
Teacher spread
0.284 · how far apart the two teachers sit on this one work
Validation status
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Abstract

During wound healing in adult mouse skin, hair follicles and then adipocytes regenerate. Adipocytes regenerate from myofibroblasts, a specialized contractile wound fibroblast. Here we study wound fibroblast diversity using single-cell RNA-sequencing. On analysis, wound fibroblasts group into twelve clusters. Pseudotime and RNA velocity analyses reveal that some clusters likely represent consecutive differentiation states toward a contractile phenotype, while others appear to represent distinct fibroblast lineages. One subset of fibroblasts expresses hematopoietic markers, suggesting their myeloid origin. We validate this finding using single-cell western blot and single-cell RNA-sequencing on genetically labeled myofibroblasts. Using bone marrow transplantation and Cre recombinase-based lineage tracing experiments, we rule out cell fusion events and confirm that hematopoietic lineage cells give rise to a subset of myofibroblasts and rare regenerated adipocytes. In conclusion, our study reveals that wounding induces a high degree of heterogeneity among fibroblasts and recruits highly plastic myeloid cells that contribute to adipocyte regeneration.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

The record

Venue
Nature Communications
Topic
Wound Healing and Treatments
Field
Medicine
Canadian institutions
Funders
National Institute of Allergy and Infectious DiseasesNational Institute of General Medical SciencesCanadian Institutes of Health ResearchCenter for Complex Biological Systems, University of California, IrvineNational Science FoundationNational Institutes of HealthNational Institute of Arthritis and Musculoskeletal and Skin DiseasesLEO Fondet
Keywords
FibroblastBiologyMyeloidMyofibroblastCell biologyHaematopoiesisProgenitor cellWound healingCellAdipocyteMolecular biologyStem cellCell cultureImmunologyGeneticsPathologyAdipose tissueMedicineFibrosis
Has abstract in OpenAlex
yes