Cell surface marker profiling of human tracheal basal cells reveals distinct subpopulations, identifies MST1/MSP as a mitogenic signal, and identifies new biomarkers for lung squamous cell carcinomas

Autor: Nadeem Moghal, Laurie Ailles, Josh Paterson, Emily Van de Laar, Nancy M Vu, Ming-Sound Tsao, Stefan Hasenoeder, Dennis Wang, Bo Ram Kim, Thomas K. Waddell, Shaf Keshavjee, Monica Clifford, Sharon Lee
Jazyk: angličtina
Předmět:
Male
Pulmonary and Respiratory Medicine
Pathology
medicine.medical_specialty
Lung Neoplasms
Time Factors
Cell
Population
Kaplan-Meier Estimate
Mice
SCID
Biology
Flow cytometry
Mice
Inbred NOD
Cell Line
Tumor
Proto-Oncogene Proteins
Biomarkers
Tumor
medicine
Animals
Humans
Cell Lineage
Progenitor cell
education
Aged
Cell Proliferation
education.field_of_study
medicine.diagnostic_test
Hepatocyte Growth Factor
Cell growth
Research
Gene Expression Profiling
Stem Cells
Receptor Protein-Tyrosine Kinases
Reproducibility of Results
Epithelial Cells
Middle Aged
respiratory system
Flow Cytometry
Prognosis
Immunohistochemistry
Molecular biology
Rats
Trachea
Gene expression profiling
medicine.anatomical_structure
Cell culture
Carcinoma
Squamous Cell
Stem cell
Signal Transduction
Stem Cell Transplantation
Zdroj: Respiratory Research
ISSN: 1465-993X
DOI: 10.1186/s12931-014-0160-8
Popis: Background The large airways of the lungs (trachea and bronchi) are lined with a pseudostratified mucociliary epithelium, which is maintained by stem cells/progenitors within the basal cell compartment. Alterations in basal cell behavior can contribute to large airway diseases including squamous cell carcinomas (SQCCs). Basal cells have traditionally been thought of as a uniform population defined by basolateral position, cuboidal cell shape, and expression of pan-basal cell lineage markers like KRT5 and TP63. While some evidence suggests that basal cells are not all functionally equivalent, few heterogeneously expressed markers have been identified to purify and study subpopulations. In addition, few signaling pathways have been identified that regulate their cell behavior. The goals of this work were to investigate tracheal basal cell diversity and to identify new signaling pathways that regulate basal cell behavior. Methods We used flow cytometry (FACS) to profile cell surface marker expression at a single cell level in primary human tracheal basal cell cultures that maintain stem cell/progenitor activity. FACS results were validated with tissue staining, in silico comparisons with normal basal cell and lung cancer datasets, and an in vitro proliferation assay. Results We identified 105 surface markers, with 47 markers identifying potential subpopulations. These subpopulations generally fell into more (~ > 13%) or less abundant (~
Databáze: OpenAIRE
Externí odkaz: