Highlights
- •
Reindeer antler velvet regenerates after wounding whereas back skin forms a scar
- •
Fibroblasts direct site-specific immune cell recruitment and differentiation
- •
Fibroblast fate reversion and absence of inflammatory signals enables regeneration
- •
Obstructing fibroblast inflammatory signals enhances skin regeneration
Summary
Graphical abstract
Keywords
Introduction
- Moore A.L.
- Marshall C.D.
- Barnes L.A.
- Murphy M.P.
- Ransom R.C.
- Longaker M.T.
Results
Antler velvet exhibits regeneration after wounding
Regenerative competence is intrinsic to velvet cells
Velvet dermis is comprised fetal-like fibroblasts
Cross-species comparisons reveal molecular hallmarks of divergent healing outcomes
- Moore A.L.
- Marshall C.D.
- Barnes L.A.
- Murphy M.P.
- Ransom R.C.
- Longaker M.T.
Fibroblast fate reversion and immunosuppression drives velvet regeneration
Fibroblast priming exacerbates inflammation and myeloid maturation to promote scar
Pro-inflammatory stromal-immune crosstalk creates a pro-fibrotic wound environment
- Raredon M.S.B.
- Yang J.
- Garritano J.
- Wang M.
- Kushnir D.
- Schupp J.C.
- Adams T.S.
- Greaney A.M.
- Leiby K.L.
- Kaminski N.
Pharmacologic recapitulation of back skin milieu ameliorates velvet regeneration
Acquisition of fibroblast inflammatory priming predetermines fibrotic repair
Intercepting mediators of fibroblast inflammatory priming enhances skin regeneration
Discussion
- Moore A.L.
- Marshall C.D.
- Barnes L.A.
- Murphy M.P.
- Ransom R.C.
- Longaker M.T.
Limitations of the study
STAR★Methods
Key resources table
REAGENT or RESOURCE | SOURCE | IDENTIFIER |
---|---|---|
Antibodies | ||
Rabbit anti-Keratin5 | Covance or Biolegend | Cat#: 905501 or PRB-160P; RRID:AB_2565050 |
Mouse anti-Ki67 | Dako | Cat# M7240; RRID:AB_2142367 |
Mouse Anti-S100A9/Calprotectin | Abcam | Cat# ab22506; RRID:AB_447111 |
Rabbit Anti-Von Willebrand Factor | Dako | Cat# A0082; RRID:AB_2315602 |
Rabbit Anti-CRABP1 | Cell signaling | Cat#13163; RRID: AB_2750569 |
Anti-mouse Alexa 488 secondary antibody | Invitrogen | Cat# A32723; RRID:AB_2633275 |
Chemicals, peptides, and recombinant proteins | ||
Serum-free DMEM (low glucose, with L-Glutamine) | Gibco™ | 11885084 |
HBSS | Gibco™ | 14175-095 |
L-Glutamine | Gibco™ | 25030081 |
Fetal Bovine Serum | Gibco™ | 12483020 |
Penicillin-streptomycin | Gibco™ | 15070063 |
Fungizone | Gibco™ | 15290018 |
Collagenase IV | Sigma-Aldrich | C5138 |
Dispase 5 | StemCell Technologies | 07913 |
Medetomidine 10mg/ml | Alberta Veterinary Laboratories (Avetlabs) | N/A |
Azaperone | Chiron | 13849.19 |
Optixcare eye lube | Aventix Animal Health | OPX-4242 |
Lidocaine HCI Injection with Preservative (2%) | Teligent Canada | DIN: 02422026, 0127AJ01 |
Meloxicam | Boehringer Ingelheim | DIN: 02330059 |
Eprinomectin | Merial (Boehringer Ingelheim) | DIN: 02450798 |
Atipamezole 10mg/ml | Alberta Veterinary Laboratories (Avetlabs) | N/A |
Paraformaldehyde (PFA) | Sigma-Aldrich | 441244 |
Clear Frozen Section Compound | VWR | 95057-838 |
Swat Original Fly Repellent Ointment | Farnam | 100532426 |
FluoSpheres™ Carboxylate-Modified Microspheres, 0.2 μm, dark red fluorescent (660/680), 2% solids | ThermoFisher | F8807 |
TGFbeta MAB (InVivoMab anti-mouse/human/rat/monkey/hamster/canine/bovine TGF-β) | Bio X Cell | BE0057-5MG-A |
TGFbeta Isotype Control (InVivoMab mouse IgG1 isotype control) | Bio X Cell | BE0083-5MG-A |
Bovine M-CSF (CSF-1) (Yeast-derived Recombinant Protein) | Kingfisher Biotech, Inc. | RP1353B-025 |
Human CXCL3 (GRO gamma) (Yeast-derived Recombinant Protein) | Kingfisher Biotech, Inc. | RP1673H-025 |
Bovine CCL2 (MCP-1) (Yeast-derived Recombinant Protein) | Kingfisher Biotech, Inc. | RP0027B-025 |
Prostaglandin D2 (PGD2) | Cayman Chemical | 12010-25 |
Midkine Inhibitor, iMDK | MilliporeSigma | 5.08052.0001 |
Recombinant Human u-Plasminogen Activator (Urokinase) | BioLegend | 755304 |
PBS | Thermo Fisher Scientific | 10010-049 |
Control chow | Plexxikon Inc | AIN-76A, D10001i |
CSF1R inhibitor | Plexxikon Inc | PLX5622, D11100404i |
CXCR4 antagonist (Plerixafor) | Tocris Bioscience | 3299 |
Dimethyl sulfoxide (DMSO) anhydrous, ≥99.9% | Sigma-Aldrich | 276855 |
Normal Goat Serum | Jackson ImmunoResearch | 005-000-121 |
Triton X-100 | Sigma-Aldrich | X100 |
Hoechst 33258 | Sigma-Aldrich, Invitrogen | 14530, H3570 |
Permafluor mounting media | Thermo Scientific | ta030FM |
Bovine Albumin Serum(BSA) Solution | Sigma-Aldrich | 19576 |
ACK Buffer | Stemcell Technologies | 07800 |
RNAlater | Thermofisher | AM7024 |
TRIzol™ | Life Technologies | 15596026 |
RNeasy | Qiagen | 74104 |
Xylene | VWR | 89370-088 |
3,3′-Diaminobenzidine (DAB) | Vector Laboratories | SK-4105 |
Elite ABC system | Vector Laboratories | PK-6100 |
Avidin/Biotin Blocking Kit | Vector Laboratories | SP-2001 |
Hematoxylin QS Counterstain | Vector Laboratories | H-3404-100 |
Critical commercial assays | ||
BD Facs Aria III | BD Biosciences | N/A |
RNAScope 2.0 HD Detection Kit | ACDBio | N/A |
10X Chromium Controller | 10X Genomics | N/A |
gentleMACS™ Octo Dissociator | Miltenyi Biotec | N/A |
Chromium Single Cell Chip A kit, 48 rnxs | 10X Genomics | 120236 |
Chromium Single cell 3′ Library & Gel beaded kit V3 and 3.1 Next GEM, 16 rnxs | 10X Genomics | 1000075; 1000128 |
Chromium i7 multiplex Kit 96 rnxs | 10X Genomics | 120262 |
Chromium Chip E Single Cell ATAC kit | 10X Genomics | 1000086 |
Chromium Single Cell ATAC library & Gel Bead Kit V1 | 10X Genomics | 1000111 |
Chromium i7 multiplex Kit N, Set A 96 rnxs | 10X Genomics | 1000084 |
Illumina NovaSeq SP, S1, S2 Flowcells | Illumina, Centre for Health Genomics and Informatics, University of Calgary | N/A |
Qubit Fluorometer | Life Technologies | N/A |
Corning® Transwell® polycarbonate membrane cell culture inserts | Corning® | CLS3415 |
Deposited data | ||
Reindeer scRNA-Seq Wound datasets | This paper | GEO: GSE142854 (SuperSeries: GSE168748) |
Reindeer scRNA-Seq PBMC datasets | This paper | GEO: GSE180653 (SuperSeries: GSE168748) |
Reindeer Bulk RNA-Seq datasets | This paper | GEO: GSE168746 (SuperSeries: GSE168748) |
Reindeer scATAC-Seq datasets | This paper | GEO: GSE176360 (SuperSeries: GSE168748) |
Velocyto-generated LOOM files from scRNA-Seq datasets | This paper | http://doi.org/10.6084/m9.figshare.14196344 |
Fetal and Adult Human Skin scRNA-Seq datasets | Reynolds, Vegh, Fletcher, Poyner et al. Science 2021
31
|
https://zenodo.org/record/4536165 https://developmentcellatlas.ncl.ac.uk/datasets/hca_skin_portal/ |
Acomys (spiny mice) versus Mus (lab mice) D0 fibroblast comparisons | GEO: GSE216723 | |
Human skin scRNA-Seq datasets | Solé-Boldo et al.
33
|
GEO: GSE130973 |
Human wound healing bulk-seq datasets | Iglesias-Bartolome et al.
54
|
GEO: GSE97615 |
Experimental models: Organisms/strains | ||
Rangifer tarandus | University of Calgary | N/A |
Mus Musculus C57BL/6 strain | University of Calgary | N/A |
Software and algorithms | ||
R Studio | https://www.rstudio.com/products/rstudio/ | Version 3.6.2-4.1.0 |
R | https://www.r-project.org/ | Version 3.6.2-4.0.5 |
Python | https://www.python.org/ | Version 3.8.5 |
Cell Ranger | 10X Genomics | Version 3.0.1 |
Cell Ranger ATAC | 10X Genomics | Version 1.2.0 |
Seurat | https://github.com/satijalab/seurat | Version 3.2.3 - 4.0.3 |
SCENIC | https://github.com/aertslab/SCENIC | Version 1.2.4 |
Connectome | https://github.com/msraredon/Connectome | Version 0.2.2 |
EnhancedVolcano | https://bioconductor.org/packages/release/bioc/html/EnhancedVolcano.html | Version 1.4.0 |
scVelo | https://github.com/theislab/scvelo | Version 0.2.3 |
pySCENIC | https://github.com/aertslab/pySCENIC | Version 0.10.4 |
CellRank | https://github.com/theislab/cellrank | Version 1.2.0 |
Nebulosa | https://github.com/powellgenomicslab/Nebulosa | Version 1.0.2 |
ggplot2 | https://cran.r-project.org/web/packages/ggplot2/index.html | Version 3.3.2; 3.1.1 |
RSEM | https://github.com/deweylab/RSEM | Version 1.3.0, 1.2.29 |
bowtie2 | https://github.com/BenLangmead/bowtie2 | Version 2.3.4.1 |
Bowtie | https://bioconductor.org/packages/release/bioc/html/Rbowtie.html | Version 1 |
EBSeq | https://www.bioconductor.org/packages/release/bioc/html/EBSeq.html | Version 1.26.0 |
Pheatmap | https://github.com/raivokolde/pheatmap | Version 1.0.12 |
RShiny | https://github.com/rstudio/shiny | Version 1.1.0 |
shinyLP | https://github.com/jasdumas/shinyLP | Version 1.1.2 |
shinyWidgets | https://github.com/dreamRs/shinyWidgets | Version 0.5.3 |
Shinythemes | https://github.com/rstudio/shinythemes | Version 1.1.2 |
CICERO | https://github.com/stjude/CICERO | Version 1.3.4.11 |
Signac | https://github.com/timoast/signac | Version 1.2.1 |
Ggforestplot | https://nightingalehealth.github.io/ggforestplot/index.html | Version 0.1.0 |
Overlap | https://www.rdocumentation.org/packages/overlap/versions/0.3.4 | Version 0.3.4 |
TOSTER | https://github.com/Lakens/TOSTER | Version 0.3.4 |
PCAtools | https://github.com/kevinblighe/PCAtools | Version 2.2.0 |
Souporcell | https://github.com/wheaton5/souporcell | Version 2 |
scPred | https://powellgenomicslab.github.io/scPred/ | Version 1.9.2 |
NICHES | https://github.com/msraredon/NICHES | Version 0.0.2 |
Nebulosa | https://github.com/powellgenomicslab/Nebulosa | Version 1.0.2 |
GOplot | https://wencke.github.io/ | Version 1.0.2 |
ggVennDiagram | https://cran.r-project.org/web/packages/ggVennDiagram/ | Version 1.0.2 |
Image J | ImageJ | N/A |
QuPath | https://qupath.readthedocs.io/ | Version 0.3 |
Olympus software | Olympus | N/A |
BSgenome.Btaurus.UCSC.bosTau9 | Bioconductor | Version 1.4.2 |
Leica software | Leica | N/A |
LC-Polscope software | PerkinElmer | openpolscope.org |
BioRender | BioRender.com | |
Other | ||
Human Protein Atlas | https://www.proteinatlas.org/ | Version 19.3 |
Reindeer Web Atlas | This paper | http://www.biernaskielab.ca/reindeer_atlas/ |
GitHub links | This paper | https://github.com/BiernaskieLab |
PDS II (polydioxanone) Suture | Ethicon Inc | Z451G |
Sutures - 0 polypropylene (0 Prolene) | Ethicon Inc | Z467H |
Resource availability
Lead contact
Materials availability
Experimental model and subject details
Animals
Method details
Skin wound creation and tissue collection
Ectopic velvet graft and wounding
In vivo velvet drug delivery
Tissue processing for single-cell genomics
Single cell RNA- and ATAC-Seq library construction and sequencing
Co-culture of reindeer skin explants or fibroblasts with peripheral leukocytes
CSF1R and CXCR4 inhibition assessed using rodent WIHN model
Sample preparation for shotgun proteomics
Quantification and statistical analysis
Immunohistochemistry and quantitative image analysis
Imaging and HF quantification
Gross wound measurements
Reference genome generation and RNA-/ATAC-Seq read alignment
Bioinformatics analysis of single-cell RNA-Seq datasets
Inferring cell–cell communication
Gene Regulatory Network inference
Reconstructing fibroblast dynamics during healing
Cross-species fibroblast state classification
Bioinformatics analysis of bulk RNA-Seq datasets
Bioinformatics analysis of single-cell ATAC-Seq datasets
Human Protein Atlas corroboration
Reindeer Atlas
Genetic demultiplexing of pooled single-cell RNA-seq datasets
Quantitative analysis of matrisome structure
High Performance Liquid Chromatography (HPLC) and Mass Spectrometry (MS)
Relative quantification and bioinformatics for proteomic analysis
Additional resources
Data and code availability
- •
Sequencing data reported in this work are available at NCBI GEO data repository (GSE168748). Mass spectrometry datasets are available at the ProteomeXchange Consortium in the PRIDE partner repository (PXD035749).
- •
Analysis code generated in this work are available at: http://doi.org/10.6084/m9.figshare.14196344 and github.com/BiernaskieLab.
- •
Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.
Acknowledgments
Author contributions
Declaration of interests
Inclusion and diversity
Supplemental information
-
Table S1. Consensus DEGs differentially expressed in reindeer velvet and fetal human fibroblasts relative to reindeer back skin and adult human fibroblasts, related to Figures 2 and 3
Genes with log-fold-change less than 0.25 or Wilcoxon rank-sum-determined two-sided p value > 0.05 were filtered out.
-
Table S2. Differentially spliced genes identified using RNA velocity grouped by tissue (velvet versus back skin) and fibroblasts subsets (Clusters 0–14), related to Figure 2
-
Table S3. Magnitude of gene expression change and frequency of fibroblasts expressing regeneration-associated markers CRABP1, MDK and SPARC, related to Figure 4
-
Table S4. A set of core DEGs distinguishing velvet and back skin fibroblasts at ground state that were differentially maintained in wound-activated fibroblasts, related to Figures 3 and 4
-
Table S5. Transcriptional signature shared between uninjured velvet and fetal human fibroblasts that are differentially maintained over the healing trajectory relative to reindeer backskin, related to Figure 3
Genes with log-fold-change less than 0.25 or Wilcoxon rank-sum-determined two-sided p value > 0.05 were filtered out.
-
Table S6. List of cell-cell signaling edges originating either from immune and vasculature-associated cells (Tables 1–4) or fibroblasts (Tables 5–8), related to Figures 5 and 6
-
Table S7. Fibroblast signaling mechanisms associated with regenerative-to-inflammatory transition in ectopic grafts, related to Figures 7 and S7
Differential ligand-receptor mechanisms were identified using ROC analysis and the table lists putative mechanisms and their classification power ranging from 0 (random) to 1 (perfect classification).
References
-
Wound repair and regeneration.Nature. 2008; 453: 314-321https://doi.org/10.1038/nature07039
-
Scarless fetal wound healing: a basic science review.Plast. Reconstr. Surg. 2010; 126: 1172-1180
-
Scarless wound healing: transitioning from fetal research to regenerative healing.Wiley Interdiscip. Rev. Dev. Biol. 2018; 7https://doi.org/10.1002/wdev.309
-
Scarless fetal skin wound healing update.Birth Defects Res. C Embryo Today. 2012; 96: 237-247https://doi.org/10.1002/bdrc.21018
-
Intrauterine wound healing in a 20 week human fetus.Virchows Arch. A Pathol. Anat. Histol. 1979; 381: 353-361https://doi.org/10.1007/BF00432477
-
Comparative regenerative mechanisms across different mammalian tissues.NPJ Regen. Med. 2018; 3: 6
-
Skin shedding and tissue regeneration in African spiny mice (Acomys).Nature. 2012; 489: 561-565https://doi.org/10.1038/nature11499
-
Distinct regulatory programs control the latent regenerative potential of dermal fibroblasts during wound healing.Cell Stem Cell. 2020; 27: 396-412.e6https://doi.org/10.1016/j.stem.2020.07.008
-
Regeneration of fat cells from myofibroblasts during wound healing.Science. 2017; 355: 748-752
-
Wnt-dependent de novo hair follicle regeneration in adult mouse skin after wounding.Nature. 2007; 447: 316-320https://doi.org/10.1038/nature05766
-
Skin wound healing in humans and mice: challenges in translational research.J. Dermatol. Sci. 2018; 90: 3-12
-
Integrated spatial multiomics reveals fibroblast fate during tissue repair.Proc. Natl. Acad. Sci. USA. 2021; 118 (e2110025118)
-
Laboratory mice born to wild mice have natural microbiota and model human immune responses.Science. 2019; 365: eaaw4361
-
Deer antlers as a model of Mammalian regeneration.Curr. Top. Dev. Biol. 2005; 67: 1-48https://doi.org/10.1016/S0070-2153(05)67001-9
-
Deer antler--a novel model for studying organ regeneration in mammals.Int. J. Biochem. Cell Biol. 2014; 56: 111-122https://doi.org/10.1016/j.biocel.2014.07.007
-
Deer Antlers: Regeneration, Function and Evolution.Academic Press, 1983
-
Regrowth of amputated velvet antlers with and without innervation.J. Exp. Zool. 1985; 234: 359-366
-
Preventing Engrailed-1 activation in fibroblasts yields wound regeneration without scarring.Science. 2021; 372: eaba2374
-
Adult skin wounds in the fetal environment heal with scar formation.Ann. Surg. 1994; 219: 65-72
-
Skin fibrosis. Identification and isolation of a dermal lineage with intrinsic fibrogenic potential.Science. 2015; 348: aaa2151
-
Comprehensive integration of single-cell data.Cell. 2019; 177: 1888-1902.e21https://doi.org/10.1016/j.cell.2019.05.031
-
Fibroblasts: origins, definitions, and functions in health and disease.Cell. 2021; 184: 3852-3872
-
Souporcell: robust clustering of single-cell RNA-seq data by genotype without reference genotypes.Nat. Methods. 2020; 17: 615-620
-
Single-cell analysis reveals fibroblast heterogeneity and myeloid-derived adipocyte progenitors in murine skin wounds.Nat. Commun. 2019; 10: 650https://doi.org/10.1038/s41467-018-08247-x
-
Dynamic regulation of retinoic acid-binding proteins in developing, adult and neoplastic skin reveals roles for beta-catenin and Notch signalling.Dev. Biol. 2008; 324: 55-67https://doi.org/10.1016/j.ydbio.2008.08.034
-
SCENIC: single-cell regulatory network inference and clustering.Nat. Methods. 2017; 14: 1083-1086https://doi.org/10.1038/nmeth.4463
-
The transcription factor Sp3 cooperates with HDAC2 to regulate synaptic function and plasticity in neurons.Cell Rep. 2017; 20: 1319-1334
-
Lef1 expression in fibroblasts maintains developmental potential in adult skin to regenerate wounds.eLife. 2020; 9: e60066https://doi.org/10.7554/eLife.60066
-
Human stem cells from the apical papilla response to bacterial lipopolysaccharide exposure and anti-inflammatory effects of nuclear factor I C.J. Endod. 2013; 39: 1416-1422https://doi.org/10.1016/j.joen.2013.07.018
-
Macrophages are necessary for epimorphic regeneration in African spiny mice.eLife. 2017; 6: e24623
-
Developmental cell programs are co-opted in inflammatory skin disease.Science. 2021; 371: eaba6500https://doi.org/10.1126/science.aba6500
-
Fetal skin wound healing.Adv. Clin. Chem. 2009; 48: 137-161
-
Single-cell transcriptomes of the human skin reveal age-related loss of fibroblast priming.Commun. Biol. 2020; 3: 188https://doi.org/10.1038/s42003-020-0922-4
-
Proteomics. Tissue-based map of the human proteome.Science. 2015; 347: 1260419https://doi.org/10.1126/science.1260419
-
Supervised classification enables rapid annotation of cell atlases.Nat. Methods. 2019; 16: 983-986
-
Onco-fetal reprogramming of endothelial cells drives immunosuppressive macrophages in hepatocellular carcinoma.Cell. 2020; 183: 377-394.e21
-
scPred: accurate supervised method for cell-type classification from single-cell RNA-seq data.Genome Biol. 2019; 20: 264
-
RNA velocity of single cells.Nature. 2018; 560: 494-498https://doi.org/10.1038/s41586-018-0414-6
-
Generalizing RNA velocity to transient cell states through dynamical modeling.Nat. Biotechnol. 2020; 38: 1408-1414https://doi.org/10.1038/s41587-020-0591-3
-
Dysfunction of hair follicle mesenchymal progenitors contributes to age-associated hair loss.Dev. Cell. 2020; 53: 185-198.e7https://doi.org/10.1016/j.devcel.2020.03.019
-
Transcriptional profiling of the adult hair follicle mesenchyme reveals R-spondin as a novel regulator of dermal progenitor function.iScience. 2020; 23: 101019https://doi.org/10.1016/j.isci.2020.101019
-
An integrated transcriptome atlas of embryonic hair follicle progenitors, their niche, and the developing skin.Dev. Cell. 2015; 34: 577-591https://doi.org/10.1016/j.devcel.2015.06.023
-
Massively parallel single-cell chromatin landscapes of human immune cell development and intratumoral T cell exhaustion.Nat. Biotechnol. 2019; 37: 925-936
-
Profiling chromatin accessibility at single-cell resolution.Genomics Proteomics Bioinformatics. 2021; 19: 172-190
-
Single-cell chromatin state analysis with Signac.Nat. Methods. 2021; 18: 1333-1341
-
CellRank for directed single-cell fate mapping.Nat. Methods. 2022; 19: 159-170https://doi.org/10.1101/2020.10.19.345983
-
Eotaxin is a natural antagonist for CCR2 and an agonist for CCR5.Blood. 2001; 97: 1920-1924https://doi.org/10.1182/blood.v97.7.1920
-
Fibroblast heterogeneity and immunosuppressive environment in human breast cancer.Cancer Cell. 2018; 33: 463-479.e10https://doi.org/10.1016/j.ccell.2018.01.011
-
A common framework of monocyte-derived macrophage activation.Sci. Immunol. 2022; 7: eabl7482
-
Single-cell transcriptome profiling reveals neutrophil heterogeneity in homeostasis and infection.Nat. Immunol. 2020; 21: 1119-1133
-
Connectome: computation and visualization of cell-cell signaling topologies in single-cell systems data.Preprint at bioRxiv. 2021; https://doi.org/10.1101/2021.01.21.427529
-
Single-cell connectomic analysis of adult mammalian lungs.Sci. Adv. 2019; 5: eaaw3851https://doi.org/10.1126/sciadv.aaw3851
-
Mapping transcriptomic vector fields of single cells.Cell. 2022; 185: 690-711.e45https://doi.org/10.1101/696724
-
Transcriptional signature primes human oral mucosa for rapid wound healing.Sci. Transl. Med. 2018; 10
-
Comprehensive visualization of cell-cell interactions in single-cell and spatial transcriptomics with NICHES.2022https://doi.org/10.1101/2022.01.23.477401
-
The neuronal repellent Slit inhibits leukocyte chemotaxis induced by chemotactic factors.Nature. 2001; 410: 948-952
-
dsRNA released by tissue damage activates TLR3 to drive skin regeneration.Cell Stem Cell. 2015; 17: 139-151
-
Ontogeny of the skin and the transition from scar-free to scarring phenotype during wound healing in the pouch young of a marsupial, Monodelphis domestica.Dev. Biol. 1995; 169: 242-260
-
Ontogeny of fetal sheep polymorphonuclear leukocyte phagocytosis.J. Pediatr. Surg. 1991; 26: 853-855
-
Wound healing in the PU, 1 Null mouse—tissue repair is not dependent on inflammatory cells.Curr. Biol. 2003; 13: 1122-1128
-
Multi-omic analysis reveals divergent molecular events in scarring and regenerative wound healing.Cell Stem Cell. 2022; 29: 315-327.e6
-
Disrupting biological sensors of force promotes tissue regeneration in large organisms.Nat. Commun. 2021; 12: 5256
-
Microenvironmental sensing by fibroblasts controls macrophage population size.Proc. Natl. Acad. Sci. USA. 2022; 119 (e2205360119)
-
Inhibition of the growth factor MDK/midkine by a novel small molecule compound to treat non-small cell lung cancer.PLoS One. 2013; 8: e71093
-
The digital slide archive: a software platform for management, integration, and analysis of histology for cancer research.Cancer Res. 2017; 77: e75-e78
-
QuPath: open source software for digital pathology image analysis.Sci. Rep. 2017; 7: 16878
-
Equivalence testing for psychological research: A tutorial.Adv. Methods Pract. Psychol. Sci. 2018; 1: 259-269
-
Estimating overlap of daily activity patterns from camera trap data.J. Agric. Biol. Environ. Stat. 2009; 14: 322-337
-
Zero-preserving imputation of single-cell RNA-seq data.Nat. Commun. 2022; 13: 192
-
Revealing the critical regulators of cell identity in the mouse cell atlas.Cell Rep. 2018; 25: 1436-1445.e3https://doi.org/10.1016/j.celrep.2018.10.045
-
Nebulosa recovers single cell gene expression signals by kernel density estimation.Bioinformatics. 2021; : btab003https://doi.org/10.1093/bioinformatics/btab003
-
RSEM: accurate transcript quantification from RNA-seq data with or without a reference genome.BMC Bioinformatics. 2011; 12: 323https://doi.org/10.1186/1471-2105-12-323
-
Fast gapped-read alignment with Bowtie 2.Nat. Methods. 2012; 9: 357-359https://doi.org/10.1038/nmeth.1923
-
EBSeq: an empirical Bayes hierarchical model for inference in RNA-seq experiments.Bioinformatics. 2013; 29: 1035-1043https://doi.org/10.1093/bioinformatics/btt087
-
Cicero predicts cis-regulatory DNA interactions from single-cell chromatin accessibility data.Mol. Cell. 2018; 71: 858-871.e8
-
Analysis of microtubule dynamics by polarized light.Methods Mol Med. 2007; 137: 111-123
-
Andromeda: a peptide search engine integrated into the MaxQuant environment.J. Proteome Res. 2011; 10: 1794-1805
-
MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification.Nat. Biotechnol. 2008; 26: 1367-1372
-
Proteome-wide identification of ubiquitin interactions using UbIA-MS.Nat. Protoc. 2018; 13: 530-550
-
Variance stabilization applied to microarray data calibration and to the quantification of differential expression.Bioinformatics. 2002; 18: S96-S104
-
BoxPlotR: a web tool for generation of box plots.Nat. Methods. 2014; 11: 121-122
-
Heterogeneity of neutrophils.Nat. Rev. Immunol. 2019; 19: 255-265
Article info
Publication history
Identification
Copyright
User license
Creative Commons Attribution – NonCommercial – NoDerivs (CC BY-NC-ND 4.0) |Permitted
For non-commercial purposes:
- Read, print & download
- Redistribute or republish the final article
- Text & data mine
- Translate the article (private use only, not for distribution)
- Reuse portions or extracts from the article in other works
Not Permitted
- Sell or re-use for commercial purposes
- Distribute translations or adaptations of the article
Elsevier's open access license policy