The respiratory endoderm develops from a small cluster of cells located on the ventral anterior foregut. This population of progenitors generates the myriad epithelial lineages required for proper lung function in adults through a complex and delicately balanced series of developmental events controlled by many critical signaling and transcription factor pathways. In the past decade, understanding of this process has grown enormously, helped in part by cell lineage fate analysis and deep sequencing of the transcriptomes of various progenitors and differentiated cell types. This review explores how these new techniques, coupled with more traditional approaches, have provided a detailed picture of development of the epithelial lineages in the lung and insight into how aberrant development can lead to lung disease.
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http://dx.doi.org/10.1146/annurev-cellbio-100814-125249 | DOI Listing |
EMBO Rep
January 2025
Division of Signal Transduction and Growth Control, German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance, Heidelberg, Germany.
Ductular reaction (DR) is the hallmark of cholestatic diseases manifested in the proliferation of bile ductules lined by biliary epithelial cells (BECs). It is commonly associated with an increased risk of fibrosis and liver failure. The receptor for advanced glycation end products (RAGE) was identified as a critical mediator of DR during chronic injury.
View Article and Find Full Text PDFCultured human embryonic stem cells (hESCs) can develop genetic anomalies that increase their susceptibility to transformation. In this study, we characterized a variant hESC (vhESC) line and investigated the molecular mechanisms leading to the drift towards a transformed state. Our findings revealed that vhESCs up-regulate EMT-specific markers, accelerate wound healing, exhibit compromised lineage differentiation, and retain pluripotency gene expression in teratomas.
View Article and Find Full Text PDFCancer Sci
December 2024
Division of Molecular Therapeutics, Aichi Cancer Center Research Institute, Nagoya, Japan.
KRAS was long deemed undruggable until the discovery of the switch-II pocket facilitated the development of specific KRAS inhibitors. Despite their introduction into clinical practice, resistance mechanisms can limit their effectiveness. Initially, tumors rely on mutant KRAS, but as they progress, they may shift to alternative pathways, resulting in intrinsic resistance.
View Article and Find Full Text PDFJ Cancer Res Clin Oncol
December 2024
Department of Breast Surgery, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde Foshan), #1, Jiazi Road, Lunjiao, Shunde District, Foshan, 528308, Guangdong Province, China.
Objective: To investigate the mechanism by which heterogeneity in breast cancer developed and acted in single-cell transcriptomes.
Methods: The composition of breast cancer based on the single-cell transcriptomes of 54,055 high-quality cells from clinical specimens of 4 malignant and 4 non-malignant patients were investigated.
Results: We identified six common expression programs and six subtype-specific expression programs form malignant epithelial cells.
J Vis Exp
December 2024
Sanford Consortium for Regenerative Medicine; Sanford Burnham Prebys Medical Discovery Institute; Department of Pediatrics, University of California, San Diego School of Medicine;
Human lung tissue is composed of an interconnected network of epithelium, mesenchyme, endothelium, and immune cells from the upper airway of the nasopharynx to the smallest alveolar sac. Interactions between these cells are crucial in lung development and disease, acting as a barrier against harmful chemicals and pathogens. Current in vitro co-culture models utilize immortalized cell lines with different biological backgrounds, which may not accurately represent the cellular milieu or interactions of the lung.
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