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Principal Investigator: Cheng-Ming Chuong
Organization: UNIVERSITY OF SOUTHERN CALIFORNIA
Fiscal Year: 2024
Award: $541,806
Funding agency: National Institute of Arthritis and Musculoskeletal and Skin Diseases
Summary (30 lines)
The long-term objective of our research is to understand the basic principles regulating the development and
regeneration of skin and its appendages, and to apply this knowledge to regenerative medicine. Recent
progress in stem cell biology has allowed the production of skin substitutes which help patients suffering from
severe skin injuries to survive. Yet, these skin substitutes lack regional specificities seen in human skin (e.g.,
scalp, face, palm, sole). The next major challenge will be to produce skins with proper region-specific
phenotypes for optimal function. While studies on region-specific skin in the mouse ear, sole and human
fibroblasts were carried out, no systemic studies have been made. Birds exhibit remarkable region-specific skin
appendages for communication, endothermy and flight, and are accessible to experimentation. We have
demonstrated how temporo-spatial expression of diffusible morphogens (Wnt, FGF, BMP and their
antagonists) can mediate epidermal-dermal interactions to generate distinct skin appendage phenotypes. Yet,
how these morphogens work at the epigenetic level, including upstream in the dermis and downstream in the
epidermis, are mostly unknown. Several recent studies provide new clues. First, the scalp is known to be a
unique skin domain with distinct appendage phenotypes in humans (terminal hairs or alopecia) and birds (crest
feathers or combs). Polish chicken variants grow feathers instead of the comb on the scalp. Using genetic
analyses, we showed a195 bp duplication in the non-coding region of HoxC10. This study offers new clues to
study how misexpression of HoxC members can act on morphogens to change combs into feathers, and how
the HoxC gene cluster is regulated. Second, using transcriptome analyses to compare dorsal and shank skin,
we recently identified a group of molecular scale-feather converters. Following this clue, we performed ATAC-
seq and high-order chromatin interactome studies to explore 3D genome organizations in feathers, scales, and
intermediate specimens. Preliminary data reveal differential chromatin accessible regions in feather / scale
inductive dermis, and in competent / committed epidermis, providing new insights into the induction of region-
specific skin appendages. Thus, the time is ripe to follow these clues to advance our understanding of skin
regional specification. We hypothesize that dermis in different skin regions exhibit distinct epigenetic profiles,
leading to specific combinatorial morphogen expressions, which guide epidermis to form specific appendage
types. In development, epidermal cells, during a time window, can exhibit bipotent competency to respond to
different dermal signals and form specific appendage types. The hypothesis will be evaluated and developed
further using a combination of classical tissue transplantation experiments and cutting-edge omics
technologies. We will focus on the scalp, dorsal and shank skins in this study but consider the fundamental
principles that would be applicable to other skin regions. The work will advance our understanding of how
region-specific skin appendages are established from the morphogen level to the epigenetic level.
Terms: <3-D><3-Dimensional><3D><ATAC sequencing><ATAC-seq><ATACseq><Affect><Alopecia><Anterior><Architecture><Assay for Transposase-Accessible Chromatin using sequencing><Aves><Avian><Baldness><Birds><CRISPR><CRISPR/Cas system><Cell Body><Cell Communication><Cell Communication and Signaling><Cell Interaction><Cell Signaling><Cell-to-Cell Interaction><Cells><ChIP Sequencing><ChIP-seq><ChIPseq><Chickens><Chromatin><Clustered Regularly Interspaced Short Palindromic Repeats><Color><Communication><Competence><Corium><Cutis><DNA Recombination><DNA Synthesis Factor><Data><Dermal><Dermal injury><Dermis><Development><Dorsal><Ear><Endothelial Cell Growth Factor><Engineering / Architecture><Epidermis><Epigenetic><Epigenetic Change><Epigenetic Mechanism><Epigenetic Process><Epithelium><Evaluation><Exhibits><Experimental Models><FGF><Face><Feathers><Fibroblast Growth Factor><Fibroblast Growth Factor Gene Family><Fibroblast Growth Regulatory Factor><Fibroblasts><Functional RNA><Future><Gallus domesticus><Gallus gallus><Gallus gallus domesticus><Gene Action Regulation><Gene Cluster><Gene Expression Regulation><Gene Regulation><Gene Regulation Process><Genetic Recombination><Genetic analyses><Genetic study><Genome><Hair><Human><Intracellular Communication and Signaling><Knowledge><Learning><Mediating><Mesenchymal><Mice><Mice Mammals><Modeling><Modern Man><Molecular><Morphogenesis><Morphology><Murine><Mus><Narration><Neural Crest><Non-Coding><Non-Coding RNA><Non-translated RNA><Noncoding RNA><Nontranslated RNA><Organizational Change><Organoids><Patients><Phenotype><Pluripotent Stem Cells><Polishes><Production><Progenitor Cells><RNA Seq><RNA sequencing><RNAseq><Recombination><Regenerative Medicine><Regulation><Research><Research Specimen><Role><Scalp><Scalp structure><Signal Transduction><Signal Transduction Systems><Signaling><Skin><Skin Substitutes><Skin injury><Skin tissue regeneration><Specific qualifier value><Specificity><Specified><Specimen><Tail><Technology><Time><Tissue Transplantation><Transplantation><Untranslated RNA><Variant><Variation><Viral><Work><antagonism><antagonist><appendage><assay for transposase accessible chromatin followed by sequencing><assay for transposase accessible chromatin seq><assay for transposase accessible chromatin sequencing><assay for transposase-accessible chromatin with sequencing><biological signal transduction><chromatin immunoprecipitation-sequencing><combinatorial><craniofacial><craniofacies><cutaneous injury><dermis regeneration><developmental><differentiation factors><epidermal injury><epidermal regeneration><epigenetic regulation><epigenetically><experiment><experimental research><experimental study><experiments><faces><facial><genetic analysis><genome scale><genome-wide><genomewide><global gene expression><global transcription profile><injuries to skin><insight><member><molecular scale><morphogenetic process><morphogenic factors><morphogens><noncoding><pluripotent progenitor><progenitor><progenitor biology><progenitor cell biology><regenerate skin><single cell analysis><skin regeneration><social role><stem and progenitor biology><stem cell biology><stem cells><three dimensional><transcriptome><transcriptome sequencing><transcriptomic sequencing><transplant>