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Scientists in the Guasch Lab have for the first time isolated and cultured cells from human sebaceous gland (called sebocytes), a specialized gland attached to the hair follicle, by mimicking the microenvironment in a petri dish.
The function of the sebaceous gland with the epidermis is to prevent the skin from dehydration and protect the body against infections and physical, chemical and thermal assaults of the environment. Using this novel method for culturing human primary sebaceous gland cells, Adrian McNairn, a former post-doctoral associate in Guasch’s lab and lead author of this paper was able to investigate which signaling pathways control the differentiation of those cells and their ability to produce lipids.
This study overcomes a major hurdle in the field of epithelial cell culture allowing new possibilities to investigate more thoroughly the sebaceous gland functions and physiology in normal and pathological conditions. Our model can not only improve our understanding of the physiology of the sebaceous gland but also can use these cells to enrich and improve the quality of engineered skin grafts: this is the central goal of our future research.
This work represents a collaborative effort between researchers in the Developmental Biology Division led by Dr. Guasch, senior author of the study, and Dr. Christopher Gordon and Armando Uribe-Rivera in the Department of Plastic Surgery, co-authors in the study.
The study was funded by L’Oreal
Other Cincinnati Children's authors include Marion Brusadelli, Christopher Gordon, Armando Uribe-Rivera.
We are addressing a novel concept in the area of the transitional epithelium associated with tumor formation: we hypothesize that this region represents a niche for stem cells receiving input from two types of epithelium, and this creates an environment sensitive to tumorigenesis. We have recently found that a population of slow-cycling cells resides in the anal epithelium at the transition with the rectum [Runck et al., Cell Cycle 2010]. We are addressing whether these cells exhibit stem cell activities and we are determining their transcriptional profile to identify candidates responsible for increased tumor formation at this region.
We are using the mouse as a model system to investigate the role of stem cells in tumor development. Our long-term goal is to understand whether skin cancers arise from stem cells and whether tumors maintain stem cells, using a combination of genetics and biochemical studies. Understanding where cancers come from and how they progress is a prerequisite to developing improved clinical treatments. Squamous cell carcinoma arises in stratified squamous epithelia of the body, and is one of the most common malignancies in humans with some of the poorest prognoses. They are frequently found at epithelial transition zones (TZs), where one type of epithelium changes to another. The underlying mechanisms for this increased tumor susceptibility are unknown. We have recently generated a mouse cancer model by deleting the essential receptor (TβRII) for TGFβ signaling in stratified epithelia. Interestingly, two tissues, the epidermis of the back skin and the anogenital epithelium, responded very differently. In the anogenital region, squamous cell carcinomas develop spontaneously between 4-9 months of age, which recapitulate epithelial cancer of the human anogenital region. We found that spontaneous squamous cell carcinoma in the TβRII deficient mice frequently arose within transitional zones between two merging but distinct epithelial tissue types. Tumor susceptibility was especially prominent at the juncture of mucosal stratified squamous epithelium of the anal canal and simple epithelial tissue of the large intestine.
Our long-term goal will address if normal resident adult tissue stem cells from the anal transitional epithelium may be a special target for carcinogenic insults.
Anorectal malformations affect one in 5,000 babies, and the etiology is unknown. We have identified specific markers for early anal epithelium that may play a crucial role in regulating epithelial morphogenesis and for establishing the boundary between the squamous epithelium of the anal canal and the simple epithelium of the rectum. We are using conditional approaches to technology in mice and human anorectal malformation samples from the Colorectal Center to investigate the role of those genes in the formation of the anal transitional epithelia. We are also actively collaborating with the Digestive Health Center.
Anorectal malformations (ARMs) occur in one in 5,000 live births. Persistent cloaca, the most complex ARM, occur in one in 50,000 live female births. It is the incomplete separation of the embryonic cloaca into urethral, vaginal and rectal openings, resulting in a common channel that opens into the perineum. The histological constituents of the common channel include the submucosa, mucosa and epithelium. The length of the common channel correlates with the prognosis in terms of bowel control, urinary control, and sexual and reproductive capabilities.
Our goal is to determine the type of epithelium found in the common channel using histological approaches on human persistent cloaca samples provided by Alberto Peña and Marc Levitt of the Colorectal Center and to determine which signaling pathways may contribute to the malformation. We are also collaborating with the Division of Pathology and Pathology Core in interpretation of the histological results.
Alberto Peña, MD
Marc Levitt, MD, and the Colorectal Center
Margaret Collins, MD, Pathology and Colorectal Center
Keith Stringer, MD, Pathology and Pathology Core
Dr. Taiwo Lawal, MD, FWACS
Department of Surgery University College Hospital PMB 5116, Ibadan, Nigeria
Phone: +234-806-961481 Email: email@example.com
click to enlarge
Proliferative sebocytes (blue nuclei) in the human sebaceous gland are in contact with dermal cells secreting fibronectin stained in red.
Ultrastructural analysis of the anorectal transitional epithelium. The dentate line separates the anal transition zone from the rectal epithelium. The dotted line denotes the presence of the basement membrane.
Slow-cycling cells at the anorectal transition zone. White arrows indicate BrdU (red) and H2B-GFP (green) label-retaining cells in the bulge (Bu) of the perianal hair follicle and in the basal layer of the anal transition zone (TZ). Higher magnification of the anal TZ, showing colocalization of H2B-GFP and BrdU-retaining cells.
Human cloaca epithelium. The simple columnar epithelium of the crypt looks morphologically normal, but an alteration in programming is evident as shown by the expression of p63 (red) in part of the basal layer.
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