title: Investigating the regulation of stem and progenitor cell mitotic progression by in situ imaging.
abstract: Genome stability relies upon efficacious chromosome congression and regulation by the spindle assembly checkpoint (SAC). The study of these fundamental mitotic processes in adult stem and progenitor cells has been limited by the technical challenge of imaging mitosis in these cells in situ. Notably, how broader physiological changes, such as dietary intake or age, affect mitotic progression in stem and/or progenitor cells is largely unknown. Using in situ imaging of C. elegans adult germlines, we describe the mitotic parameters of an adult stem and progenitor cell population in an intact animal. We find that SAC regulation in germline stem and progenitor cells is distinct from that found in early embryonic divisions and is more similar to that of classical tissue culture models. We further show that changes in organismal physiology affect mitotic progression in germline stem and progenitor cells. Reducing dietary intake produces a checkpoint-dependent delay in anaphase onset, and inducing dietary restriction when the checkpoint is impaired increases the incidence of segregation errors in mitotic and meiotic cells. Similarly, developmental aging of the germline stem and progenitor cell population correlates with a decline in the rate of several mitotic processes. These results provide the first in vivo validation of models for SAC regulation developed in tissue culture systems and demonstrate that several fundamental features of mitotic progression in adult stem and progenitor cells are highly sensitive to organismal physiological changes.
authors.affiliation: Institute of Research in Immunology and Cancer (IRIC), Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, QC H3C 3J7, Canada.
authors.forename: Abigail R
authors.initials: AR
authors.lastname: Gerhold
authors.affiliation: Institute of Research in Immunology and Cancer (IRIC), Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, QC H3C 3J7, Canada.
authors.forename: Joël
authors.initials: J
authors.lastname: Ryan
authors.affiliation: Institute of Research in Immunology and Cancer (IRIC), Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, QC H3C 3J7, Canada.
authors.forename: Julie-Nathalie
authors.initials: JN
authors.lastname: Vallée-Trudeau
authors.affiliation: Institute of Research in Immunology and Cancer (IRIC), Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, QC H3C 3J7, Canada.
authors.forename: Jonas F
authors.initials: JF
authors.lastname: Dorn
authors.affiliation: Institute of Research in Immunology and Cancer (IRIC), Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, QC H3C 3J7, Canada; Department of Pathology and Cell Biology, Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, QC H3C 3J7, Canada. Electronic address: jc.labbe@umontreal.ca.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Labbé
authors.affiliation: Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: pmaddox@unc.edu.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Maddox
mesh_terms: D053687:Adult Stem Cells / Q000502:physiology*; D000818:Animals; D017173:Caenorhabditis elegans; D005508:Food Deprivation; D049452:Green Fluorescent Proteins; D006706:Homeostasis; D059566:M Phase Cell Cycle Checkpoints; D008938:Mitosis
chemical_list: D049452:Green Fluorescent Proteins