Transcriptome Profiling and Differential Gene Expression in Canine Microdissected Anagen and Telogen Hair Follicles and Interfollicular Epidermis

The transcriptome profile and differential gene expression in telogen and late anagen microdissected hair follicles and the interfollicular epidermis of healthy dogs was investigated by using RNAseq. The genes with the highest expression levels in each group were identified and genes known from studies in other species to be associated with structure and function of hair follicles and epidermis were evaluated. Transcriptome profiling revealed that late anagen follicles expressed mainly keratins and telogen follicles expressed GSN and KRT15. The interfollicular epidermis expressed predominately genes encoding for proteins associated with differentiation. All sample groups express genes encoding for proteins involved in cellular growth and signal transduction. The expression pattern of skin-associated genes in dogs is similar to humans. Differences in expression compared to mice and humans include BMP2 expression mainly in telogen and high KRT17 expression in the interfollicular epidermis of dogs. Our data provide the basis for the investigation of the structure and function of canine skin or skin disease and support the use of dogs as a model for human cutaneous disease by assigning gene expression to specific tissue states.

[1]  R. Paus,et al.  Deciphering the molecular morphology of the human hair cycle: Wnt signalling during the telogen–anagen transformation , 2020, The British journal of dermatology.

[2]  T. Leeb,et al.  ATP2A2 SINE Insertion in an Irish Terrier with Darier Disease and Associated Infundibular Cyst Formation , 2020, Genes.

[3]  Jinquan Li,et al.  Exploring differentially expressed genes between anagen and telogen secondary hair follicle stem cells from the Cashmere goat (Capra hircus) by RNA-Seq , 2020, PloS one.

[4]  K. Plath,et al.  Defining transcriptional signatures of human hair follicle cell states. , 2020, The Journal of investigative dermatology.

[5]  T. Leeb,et al.  Abnormal keratinocyte differentiation in the nasal planum of Labrador Retrievers with hereditary nasal parakeratosis (HNPK) , 2020, PloS one.

[6]  W. Bai,et al.  m6A Methylation Analysis of Differentially Expressed Genes in Skin Tissues of Coarse and Fine Type Liaoning Cashmere Goats , 2020, Frontiers in Genetics.

[7]  E. Ostrander,et al.  Whole Genome Analysis of a Single Scottish Deerhound Dog Family Provides Independent Corroboration That a SGK3 Coding Variant Leads to Hairlessness , 2019, G3: Genes, Genomes, Genetics.

[8]  T. Leeb,et al.  A missense variant in the NSDHL gene in a Chihuahua with a congenital cornification disorder resembling inflammatory linear verrucous epidermal nevi. , 2019, Animal genetics.

[9]  A. Tosti,et al.  Genetic Hair Disorders: A Review , 2019, Dermatology and Therapy.

[10]  Randle Aaron M. Villanueva,et al.  ggplot2: Elegant Graphics for Data Analysis (2nd ed.) , 2019, Measurement: Interdisciplinary Research and Perspectives.

[11]  H. Lohi,et al.  A frameshift insertion in SGK3 leads to recessive hairlessness in Scottish Deerhounds: a candidate gene for human alopecia conditions , 2019, Human Genetics.

[12]  M. Heller,et al.  Bald thigh syndrome in sighthounds—Revisiting the cause of a well-known disease , 2019, PloS one.

[13]  L. Chevallier,et al.  NIPAL4 deletion identified in an American Bully with autosomal recessive congenital ichthyosis and response to topical therapy , 2019, Veterinary medicine and science.

[14]  Shaolong Zhang,et al.  Keratin 17 in disease pathogenesis: from cancer to dermatoses , 2018, The Journal of pathology.

[15]  Jinquan Li,et al.  Transcriptomic analysis reveals critical genes for the hair follicle of Inner Mongolia cashmere goat from catagen to telogen , 2018, PloS one.

[16]  T. Leeb,et al.  A frameshift variant in the EDA gene in Dachshunds with X-linked hypohidrotic ectodermal dysplasia. , 2018, Animal genetics.

[17]  D. Campbell,et al.  Taking the lead - how keratinocytes orchestrate skin T cell immunity. , 2018, Immunology letters.

[18]  T. Leeb,et al.  A splice site variant in the SUV39H2 gene in Greyhounds with nasal parakeratosis. , 2018, Animal genetics.

[19]  Jessica M. Hoffman,et al.  The companion dog as a model for human aging and mortality , 2018, Aging cell.

[20]  C. Ambrósio,et al.  In vitro identification of a stem cell population from canine hair follicle bulge region. , 2018, Tissue & cell.

[21]  S. Joost,et al.  Single cell transcriptomics suggest that human adipocyte progenitor cells constitute a homogeneous cell population , 2017, Stem Cell Research & Therapy.

[22]  T. Leeb,et al.  Novel insights into the pathways regulating the canine hair cycle and their deregulation in alopecia X , 2017, PloS one.

[23]  T. Olivry,et al.  Translational Animal Models of Atopic Dermatitis for Preclinical Studies

 , 2017, The Yale journal of biology and medicine.

[24]  J. Fischer,et al.  Inherited Nonsyndromic Ichthyoses: An Update on Pathophysiology, Diagnosis and Treatment , 2017, American Journal of Clinical Dermatology.

[25]  T. Leeb,et al.  A Large Deletion in the NSDHL Gene in Labrador Retrievers with a Congenital Cornification Disorder , 2017, G3: Genes, Genomes, Genetics.

[26]  H. Lohi,et al.  Nonsense variant in COL7A1 causes recessive dystrophic epidermolysis bullosa in Central Asian Shepherd dogs , 2017, PloS one.

[27]  T. Leeb,et al.  A de novo variant in the ASPRV1 gene in a dog with ichthyosis , 2017, PLoS genetics.

[28]  T. Leeb,et al.  Genetic testing in veterinary dermatology , 2017, Veterinary dermatology.

[29]  P. Henthorn,et al.  Epidermolysis bullosa simplex in sibling Eurasier dogs is caused by a PLEC non‐sense variant , 2017, Veterinary dermatology.

[30]  P. Henthorn,et al.  A Defect in NIPAL4 Is Associated with Autosomal Recessive Congenital Ichthyosis in American Bulldogs , 2017, PloS one.

[31]  W. Kim,et al.  Distinct expression profile of stem cell markers, LGR5 and LGR6, in basaloid skin tumors , 2017, Virchows Archiv.

[32]  Maria Kasper,et al.  Single-Cell Transcriptomics Reveals that Differentiation and Spatial Signatures Shape Epidermal and Hair Follicle Heterogeneity , 2016, Cell systems.

[33]  C. Drögemüller,et al.  A Splice Defect in the EDA Gene in Dogs with an X-Linked Hypohidrotic Ectodermal Dysplasia (XLHED) Phenotype , 2016, G3: Genes, Genomes, Genetics.

[34]  Y. Miao,et al.  Expression of matrix metalloproteinases and tissue inhibitor of matrix metalloproteinases in the hair cycle , 2016, Experimental and therapeutic medicine.

[35]  M. Hewicker-Trautwein,et al.  Congenital Ichthyosis in 14 Great Dane Puppies With a New Presentation , 2016, Veterinary pathology.

[36]  Xiaolong Wang,et al.  Comparative Transcriptome Analysis of Fetal Skin Reveals Key Genes Related to Hair Follicle Morphogenesis in Cashmere Goats , 2016, PloS one.

[37]  M. Welle,et al.  Spatial Distribution of Stem Cell-Like Keratinocytes in Dissected Compound Hair Follicles of the Dog , 2016, PloS one.

[38]  M. Welle,et al.  Stem Cell-Associated Marker Expression in Canine Hair Follicles , 2016, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[39]  M. Hewicker-Trautwein,et al.  A Novel SLC27A4 Splice Acceptor Site Mutation in Great Danes with Ichthyosis , 2015, PloS one.

[40]  S. Pittaluga,et al.  Hair follicle-derived IL-7 and IL-15 mediate skin-resident memory T cell homeostasis and lymphoma , 2015, Nature Medicine.

[41]  K. Credille,et al.  Autosomal Recessive Congenital Ichthyosis in American Bulldogs Is Associated With NIPAL4 (ICHTHYIN) Deficiency , 2015, Veterinary pathology.

[42]  B. Hallström,et al.  Expression of Human Skin-Specific Genes Defined by Transcriptomics and Antibody-Based Profiling , 2015, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[43]  W. Huber,et al.  Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2 , 2014, Genome Biology.

[44]  Paul Theodor Pyl,et al.  HTSeq – A Python framework to work with high-throughput sequencing data , 2014, bioRxiv.

[45]  Albert Zlotnik,et al.  The top skin-associated genes: a comparative analysis of human and mouse skin transcriptomes , 2014, Biological chemistry.

[46]  C. Drögemüller,et al.  A Mutation in the FAM83G Gene in Dogs with Hereditary Footpad Hyperkeratosis (HFH) , 2014, PLoS genetics.

[47]  R. Paus,et al.  The role of hair follicle immune privilege collapse in alopecia areata: status and perspectives. , 2013, Journal of Investigative Dermatology Symposium Proceedings.

[48]  C. Drögemüller,et al.  A Mutation in the SUV39H2 Gene in Labrador Retrievers with Hereditary Nasal Parakeratosis (HNPK) Provides Insights into the Epigenetics of Keratinocyte Differentiation , 2013, PLoS genetics.

[49]  R. Nusse,et al.  Wnt signaling in skin development, homeostasis, and disease. , 2013, Cold Spring Harbor perspectives in biology.

[50]  T. Tumbar,et al.  Hairy tale of signaling in hair follicle development and cycling. , 2012, Seminars in cell & developmental biology.

[51]  Keisuke Nagao,et al.  Stress-induced production of chemokines by hair follicles regulates the trafficking of dendritic cells in skin , 2012, Nature Immunology.

[52]  T. Olivry,et al.  Deficient Plakophilin-1 Expression Due to a Mutation in PKP1 Causes Ectodermal Dysplasia-Skin Fragility Syndrome in Chesapeake Bay Retriever Dogs , 2012, PloS one.

[53]  B. Overduin The European Nucleotide Archive (ENA) , 2012 .

[54]  F. Guscetti,et al.  The canine hair cycle - a guide for the assessment of morphological and immunohistochemical criteria. , 2011, Veterinary dermatology.

[55]  V. Horsley,et al.  Adipocyte Lineage Cells Contribute to the Skin Stem Cell Niche to Drive Hair Cycling , 2011, Cell.

[56]  A. Christiano,et al.  Niche Crosstalk: Intercellular Signals at the Hair Follicle , 2011, Cell.

[57]  P. Maini,et al.  Self-Organizing and Stochastic Behaviors During the Regeneration of Hair Stem Cells , 2011, Science.

[58]  Fiona M Watt,et al.  Cell-extracellular matrix interactions in normal and diseased skin. , 2011, Cold Spring Harbor perspectives in biology.

[59]  M. Sakaguchi,et al.  Expression of REIC/Dkk‐3 in normal and hyperproliferative epidermis , 2011, Experimental dermatology.

[60]  E. Fuchs,et al.  Dynamics between Stem Cells, Niche, and Progeny in the Hair Follicle , 2011, Cell.

[61]  E. Ostrander,et al.  An insertion in the RSPO2 gene correlates with improper coat in the Portuguese water dog. , 2010, The Journal of heredity.

[62]  Tetsuro Kobayashi,et al.  Canine follicle stem cell candidates reside in the bulge and share characteristic features with human bulge cells. , 2010, The Journal of investigative dermatology.

[63]  H. Clevers,et al.  Lgr6 Marks Stem Cells in the Hair Follicle That Generate All Cell Lineages of the Skin , 2010, Science.

[64]  R. Su,et al.  Characterization of BMP2 gene expression in embryonic and adult Inner Mongolia Cashmere goat (Capra hircus) hair follicles , 2009 .

[65]  Hadley Wickham,et al.  ggplot2 - Elegant Graphics for Data Analysis (2nd Edition) , 2017 .

[66]  Tetsuro Kobayashi,et al.  Canine hair-follicle keratinocytes enriched with bulge cells have the highly proliferative characteristic of stem cells. , 2009, Veterinary dermatology.

[67]  M. Welle,et al.  The keratinocyte in epidermal renewal and defence. , 2009, Veterinary dermatology.

[68]  T. Tumbar,et al.  Distinct self-renewal and differentiation phases in the niche of infrequently dividing hair follicle stem cells. , 2009, Cell stem cell.

[69]  D. Hohl,et al.  Transglutaminase 1‐deficient recessive lamellar ichthyosis associated with a LINE‐1 insertion in Jack Russell terrier dogs , 2009, The British journal of dermatology.

[70]  Hans Clevers,et al.  Lgr5 marks cycling, yet long-lived, hair follicle stem cells , 2008, Nature Genetics.

[71]  K. Lindblad-Toh,et al.  A Mutation in Hairless Dogs Implicates FOXI3 in Ectodermal Development , 2008, Science.

[72]  E. Fuchs,et al.  Hair follicle stem cells are specified and function in early skin morphogenesis. , 2008, Cell stem cell.

[73]  Cheng-Ming Chuong,et al.  Complex hair cycle domain patterns and regenerative hair waves in living rodents. , 2008, The Journal of investigative dermatology.

[74]  Ruth E. Baker,et al.  Cyclic dermal BMP signalling regulates stem cell activation during hair regeneration , 2008, Nature.

[75]  Youping Deng,et al.  GeneVenn - A web application for comparing gene lists using Venn diagrams , 2007, Bioinformation.

[76]  Elaine Fuchs,et al.  Scratching the surface of skin development , 2007, Nature.

[77]  Elaine Fuchs,et al.  Epidermal stem cells of the skin. , 2006, Annual review of cell and developmental biology.

[78]  N. Romani,et al.  Epidermal Langerhans cells--changing views on their function in vivo. , 2006, Immunology letters.

[79]  R. Paus,et al.  Learning from nudity: lessons from the nude phenotype , 2005, Experimental dermatology.

[80]  K. Credille,et al.  Mild recessive epidermolytic hyperkeratosis associated with a novel keratin 10 donor splice‐site mutation in a family of Norfolk terrier dogs , 2005, The British journal of dermatology.

[81]  P. Henthorn,et al.  Mutation identification in a canine model of X-linked ectodermal dysplasia , 2005, Mammalian Genome.

[82]  Masashi Suzuki,et al.  Comprehensive analysis of FGF and FGFR expression in skin: FGF18 is highly expressed in hair follicles and capable of inducing anagen from telogen stage hair follicles. , 2005, The Journal of investigative dermatology.

[83]  J. Ortonne,et al.  Inherited junctional epidermolysis bullosa in the German Pointer: establishment of a large animal model. , 2005, The Journal of investigative dermatology.

[84]  J. Schweizer,et al.  Type II epithelial keratin 6hf (K6hf) is expressed in the companion layer, matrix, and medulla in anagen-stage hair follicles. , 2003, The Journal of investigative dermatology.

[85]  S. Lyle,et al.  Keratin 15 promoter targets putative epithelial stem cells in the hair follicle bulge. , 2003, The Journal of investigative dermatology.

[86]  J. Ortonne,et al.  Genetic correction of canine dystrophic epidermolysis bullosa mediated by retroviral vectors. , 2003, Human molecular genetics.

[87]  R. Tennant,et al.  Enrichment for living murine keratinocytes from the hair follicle bulge with the cell surface marker CD34. , 2003, The Journal of investigative dermatology.

[88]  X. Tong,et al.  Keratin 17 null mice exhibit age- and strain-dependent alopecia. , 2002, Genes & development.

[89]  F. Watt The stem cell compartment in human interfollicular epidermis. , 2002, Journal of dermatological science.

[90]  Michael A Rogers,et al.  HOXC13 Is Involved in the Regulation of Human Hair Keratin Gene Expression* , 2002, The Journal of Biological Chemistry.

[91]  Sarah E. Millar,et al.  Characterization of Wnt gene expression in developing and postnatal hair follicles and identification of Wnt5a as a target of Sonic hedgehog in hair follicle morphogenesis , 2001, Mechanisms of Development.

[92]  T. Boehm,et al.  Whn and mHa3 are components of the genetic hierarchy controlling hair follicle differentiation , 1999, Mechanisms of Development.

[93]  J. Brissette,et al.  Ectopic expression of the nude gene induces hyperproliferation and defects in differentiation: implications for the self-renewal of cutaneous epithelia. , 1999, Developmental biology.

[94]  S. Eichmüller,et al.  Keratin 17 gene expression during the murine hair cycle. , 1997, The Journal of investigative dermatology.

[95]  R. Paus,et al.  Is alopecia areata an autoimmune-response against melanogenesis-related proteins, exposed by abnormal MHC class I expression in the anagen hair bulb? , 1993, The Yale journal of biology and medicine.

[96]  E. Fuchs,et al.  Expression of keratin K14 in the epidermis and hair follicle: insights into complex programs of differentiation , 1989, The Journal of cell biology.

[97]  K M Halprin,et al.  EPIDERMAL “TURNOVER TIME”—A RE‐EXAMINATION , 1972, The British journal of dermatology.

[98]  T. Lechler,et al.  Cell adhesion in epidermal development and barrier formation. , 2015, Current topics in developmental biology.

[99]  P. Rompolas,et al.  Stem cell dynamics in the hair follicle niche. , 2014, Seminars in cell & developmental biology.

[100]  R Core Team,et al.  R: A language and environment for statistical computing. , 2014 .

[101]  M. Morasso,et al.  To grow or not to grow: hair morphogenesis and human genetic hair disorders. , 2014, Seminars in cell & developmental biology.

[102]  Brad T. Sherman,et al.  Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources , 2008, Nature Protocols.

[103]  R. Paus,et al.  A 'hairy' privilege. , 2005, Trends in immunology.

[104]  F. Galibert,et al.  Nature Genetics Advance Online Publication Pnpla1 Mutations Cause Autosomal Recessive Congenital Ichthyosis in Golden Retriever Dogs and Humans , 2022 .