Project description:Microarray analysis was used to compare the transcriptome of esophageal submucosal gland (ESMG) derived spheroids in culture relative to squamous epithelium and fresh ESMGs.
Project description:The airway epithelium is in contact with the environment and therefore constantly at risk for injury. Basal cells have been found to repair the surface epithelium, but the contribution of other stem cell populations to airway epithelial repair have not been identified. We demonstrated that airway submucosal gland duct cells, in addition to basal cells, survived severe hypoxic-ischemic injury. We developed a method to isolate duct cells from the airway. In vitro and in vivo models were used to compare the self-renewal and differentiation potential of duct cells and basal cells. We found that only duct cells were capable of regenerating submucosal gland tubules and ducts, as well as the surface epithelium overlying the submucosal glands. This is of importance to the field of lung regeneration as determining the repairing cell populations could lead to the identification of novel therapeutic targets and cell-based therapies for patients with airway diseases.
Project description:The airway epithelium is in contact with the environment and therefore constantly at risk for injury. Basal cells have been found to repair the surface epithelium, but the contribution of other stem cell populations to airway epithelial repair have not been identified. We demonstrated that airway submucosal gland duct cells, in addition to basal cells, survived severe hypoxic-ischemic injury. We developed a method to isolate duct cells from the airway. In vitro and in vivo models were used to compare the self-renewal and differentiation potential of duct cells and basal cells. We found that only duct cells were capable of regenerating submucosal gland tubules and ducts, as well as the surface epithelium overlying the submucosal glands. This is of importance to the field of lung regeneration as determining the repairing cell populations could lead to the identification of novel therapeutic targets and cell-based therapies for patients with airway diseases. Murine proximal airway duct and basal cells were isolated from 8-12 week old male and female mice and FACS sorted. Each sample contains cells that were sorted from a different pool of 10-15 C57Bl/6 mice. RNA was extracted, labeled, and hybridized to Affymetrix Mouse Genome 430 2.0 Array (GPL1261)
Project description:Outputs from single-cell RNA-seq sequenced reads from isolated mouse epithelial cells from homeostatic submucosal glands and Naphthalene-injured surface epithelium of adult mouse airway (P70)
Project description:This study was designed to identify genes aberrantly expressed in esophageal squamous cell carcinoma (ESCC) cells. Three esophageal squamous cell carcinoma-derived cell lines and one normal human esophageal squamous cell line were analyzed.
Project description:We analyzed ChIP-seq, chromatin accessibility and RNA-seq across mouse esophageal squamous organoids and human esophageal squamous cell cancer
Project description:We analyzed ChIP-seq, chromatin accessibility and RNA-seq across mouse esophageal squamous organoids and human esophageal squamous cell cancer
Project description:Profiles of esophageal squamous cell carcinoma and normal esophageal normal epithelium normal cell line. Analysis provides validation of novel microRNA targets prediction algorithms. esophageal squamous cell carcinoma:14, normal epithelium cell:2
Project description:Tracheoesophageal disorders and diseases are prevalent in humans such that an organoid model of human esophagus could be greatly beneficial. We therefore established a three-dimensional esophageal organoid culture system through the directed differentiation of human pluripotent stem cells (hPSCs). We identified that sequential manipulation of several signaling pathways resulted in patterning of definitive endoderm to dorsal anterior foregut spheroids (dAFGs). Outgrowth of dAFGs for 1-2 months resulted in human esophageal organoids (HEOs) with a stratified squamous epithelium comparable to a late gestation mouse embryonic esophagus. These 1 and 2 month old HEOs were harvested for RNA to transcriptionally profile and compare them to profiles of esophageal tissue biopsies and keratinocytes. We then used HEOs and mouse embryos to identify how SOX2 mediates separation of the esophageal and respiratory lineages and found that loss of endodermal Sox2 results in complete esophageal agenesis. Using a SOX2 CRISPR interference iPS line, we generated dorsal and ventral anterior foregut progenitors (by manipulating BMP signaling) with or without SOX2-knockdown. At the transcriptional level, SOX2 acts to promote esophageal specification in both mice and humans in part by inhibiting Wnt signaling in the dorsal AFG and promoting survival of esophageal epithelium. In addition to this use of hPSC-derived esophageal organoids to study development, HEOs can be used for future studies of esophageal pathologies, such as Barrett’s metaplasia and carcinoma.
