title: A method to identify tissue cell subpopulations with distinct multi-molecular profiles from data on co-localization of two markers at a time: the case of sensory ganglia.
abstract: BACKGROUND
  Most biological tissues are characterized by high morphological and functional cell heterogeneity. To investigate this heterogeneity at the molecular level, scientists have tried to associate specific sets of molecular markers (molecular profiles) to functionally distinct cell subpopulations, evaluating their expression using immunochemistry and in situ hybridization techniques.
  
  
  METHODS
  We propose here a novel analysis that allows the estimation of the frequency of cells expressing distinct molecular profiles starting from data on the co-expression of two markers at a time. In order to facilitate the application of the proposed analysis, we developed and make available a user-friendly window-based software.
  
  
  RESULTS
  We successfully applied the analytical method to experimental data from adult rat sensory neurons. In a first application we subgrouped DRG neurons in 11 subpopulations on the basis of the co-expression of 6 molecular markers (the TRPs type V1, A1, and M8 and the trks type A, B, and C). In a second application we found that while rat DRG have significant frequencies of peptidergic/IB4-negative and non-peptidergic/IB4-positive nociceptors, rat TG neurons lack almost completely these two subpopulations.
  
  
  METHODS
  The analytical method here proposed overcomes the limitations of the presently available experimental techniques, most of which can assess the co-expression of only few molecular markers at a time.
  
  
  CONCLUSIONS
  This new method will allow a better understanding of the molecular and cellular heterogeneity of tissues in normal and pathological conditions.
authors.affiliation: Dipartimento di Chimica, Biologia e Biotecnologie, Universita' di Perugia, via Pascoli 1, Perugia, Italy. Electronic address: luigi.catacuzzeno@unipg.it.
authors.forename: Lugi
authors.initials: L
authors.lastname: Catacuzzeno
authors.affiliation: Dipartimento di Chimica, Biologia e Biotecnologie, Universita' di Perugia, via Pascoli 1, Perugia, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Sforna
authors.affiliation: Dipartimento di Medicina Sperimentale, Sezione di Fisiologia e Biochimica, Universita' di Perugia, Perugia, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: D'Adamo
authors.affiliation: Dipartimento di Medicina Sperimentale, Sezione di Fisiologia e Biochimica, Universita' di Perugia, Perugia, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Pessia
authors.affiliation: Dipartimento di Chimica, Biologia e Biotecnologie, Universita' di Perugia, via Pascoli 1, Perugia, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Franciolini
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000166:cytology*; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000378:metabolism*; D012984:Software; D050051:Transient Receptor Potential Channels / Q000378:metabolism
chemical_list: D015415:Biomarkers; D050051:Transient Receptor Potential Channels; D020794:Receptor Protein-Tyrosine Kinases
keywords: Immunocytochemistry; Immunohistochemistry; In situ hybridization; Molecular profile; Sensory neurons; Tissue cell subpopulations