Search

Summary: Perturbations in the transcriptional programs specifying epidermal differentiation cause diverse skin pathologies ranging from impaired barrier function to inflammatory skin disease. However, the global scope and organization of this complex cellular program remain undefined. Here we report single-cell RNA sequencing profiles of 92,889 human epidermal cells from 9 normal and 3 inflamed skin samples. Transcriptomics-derived keratinocyte subpopulations reflect classic epidermal strata but also sharply compartmentalize epithelial functions such as cell-cell communication, inflammation, and WNT pathway modulation. In keratinocytes, ∼12% of assessed transcript expression varies in coordinate patterns, revealing undescribed gene expression programs governing epidermal homeostasis. We also identify molecular fingerprints of inflammatory skin states, including S100 activation in the interfollicular epidermis of normal scalp, enrichment of a CD1C+CD301A+ myeloid dendritic cell population in psoriatic epidermis, and IL1βhiCCL3hiCD14+ monocyte-derived macrophages enriched in foreskin. This compendium of RNA profiles provides a critical step toward elucidating epidermal diseases of development, differentiation, and inflammation. : Cheng et al. report single-cell RNA sequencing of normal and inflamed human epidermis, revealing a discrete set of specialized keratinocytes that exhibit a distinct composition at different anatomic sites. Myeloid dendritic cells and macrophages also vary sharply with epidermal anatomic site and inflammation, indicating dynamic programming of antigen-presenting cells. Keywords: epidermis, single-cell RNA-seq, keratinocyte, skin

Breast reconstruction is offered to women undergoing mastectomy or breast conservation, given its safe nature and highly aesthetic reconstructive outcomes. Breast implants are safe, offer flexibility of sizes and projections, and shorter recovery. Autologous flaps allow women to avoid prosthetic devices, using skin and fat to replace breast tissue. The increasing frequency of nipple-sparing mastectomy, autologous fat grafting, use of acellular dermal matrices, and prepectoral prosthetic reconstruction have enhanced aesthetic outcomes. Breast conservation outcomes have been enhanced by immediate oncoplastic breast reconstruction to reduce the risks of contour deformities and breast asymmetry, and maintain excellent, oncologically safe, aesthetic outcomes.

Open coronary arterial bypass grafting (CABG) procedures are inherently risky in regards to the healing capacity of the subsequent sternal wound. Patients often have underlying risk factors for poor healing and the procedure itself often reduces vascularity to the anterior chest with internal mammary artery (IMA) dissection. Currently unrelated is the surgical delay procedure. It is a well-established technique for augmenting vascularity and ultimately tissue survival. It involves partial disruption of the blood supply to a flap for a period of time prior to fully elevating the flap (usually between 3 and 21 days). Recently, endoscopic robotic IMA dissection has become possible as a part of totally endoscopic CABGs for left-sided vessel disease. We are proposing a new technique, using surgical delay for patients who require open sternotomies for CABGS to reduce the rate of postoperative sternal wound complications. To delay the CABG, the majority of a robotic internal IMA dissection would be performed prior to an open CABG via a midline sternotomy. We hypothesize that this may decrease sternal wound complication rates. Potential pitfalls include consequences of disrupting the normal anatomic location of the IMAs and causing inflammation before the open CABG. Animal models will be the next step, as they will evaluate the feasibility of the delay as well as help to determine the optimal timing for the procedure.

Summary Identification of human satellite cells that fulfill muscle stem cell criteria is an unmet need in regenerative medicine. This hurdle limits understanding how closely muscle stem cell properties are conserved among mice and humans and hampers translational efforts in muscle regeneration. Here, we report that PAX7 satellite cells exist at a consistent frequency of 2–4 cells/mm of fiber in muscles of the human trunk, limbs, and head. Xenotransplantation into mice of 50–70 fiber-associated, or 1,000–5,000 FACS-enriched CD56+/CD29+ human satellite cells led to stable engraftment and formation of human-derived myofibers. Human cells with characteristic PAX7, CD56, and CD29 expression patterns populated the satellite cell niche beneath the basal lamina on the periphery of regenerated fibers. After additional injury, transplanted satellite cells robustly regenerated to form hundreds of human-derived fibers. Together, these findings conclusively delineate a source of bona-fide endogenous human muscle stem cells that will aid development of clinical applications., Highlights • CD56 and CD29 mark PAX7 satellite cells in diverse human muscles • Transplanted human satellite cells engraft, self-renew, and regenerate • Human adult muscle stem cells reside within the CD56+/CD29+ satellite cell pool, In this article Pomerantz and colleagues demonstrate that human skeletal muscle stem cells reside within the satellite cell pool at similar frequencies in diverse adult muscles and engraft, populate the stem cell niche, and regenerate after transplantation.

Introduction With the rise in childhood obesity, an increase in the number of patients seeking adolescent breast reduction has been appreciated. This study examines our experience with presenting symptoms, techniques, and both surgical and pathologic outcomes for reduction mammaplasty in the adolescent population. Methods Medical records of 76 consecutive patients under 18 years of age who underwent reduction mammaplasty over a 10 year period were identified and reviewed for BMI, symptoms, comorbidities, cancer history, surgical technique, resection weight, pathologic findings, and complications. Pathology costs were determined from billing records. Results Operative indications included neck, back, and/or shoulder pain (75%), intertrigo (8%), shoulder grooving (17%), difficulty finding bras (8%) and participating in sports (9%), and social distress (24%). Average BMI was 31 kg/m 2 and 65% of children were obese (BMI > 30). Surgical techniques included Wise pattern (93%) and superior pedicle (7%). Complications occurred in 8 patients (10.5%). Pathologic examination yielded no cancers with 80% normal or mildly fibrotic and 20% benign histology. Per breast reduction specimen, pathology internal costs and external costs by Medicare data averaged $65 and $118, respectively. Conclusions Adolescent mammaplasty patients present symptoms mirroring those of the adult population but also exhibit greater obesity, physical strain, social distress, and comorbid psychiatric disorders. Literature reports similar complication rates for adults as we found in our adolescent population. We recommend that surgeons strongly consider reduction mammaplasty in the carefully selected adolescent with macromastia, with realistic expectations and complications in this burgeoning group. Routine pathologic examination, however, is not a cost effective goal.