University of Dundee

Discovery Lecture - "Building muscles: from somites to muscular dystrophies"

Event Date: 
Monday, June 3, 2019 - 12:00 to 13:00
Event Location: 
MSI Small Lecture Theatre
Host: 
Professor Kim Dale FRSB
Event Speaker: 
Professor Olivier Pourquie
Institution: 
Department of Genetics, Harvard Medical School and Department of Pathology, Brigham and Women’s Hospital, Boston, Massachusetts, USA
Event Type: 
Discovery Lecture
Share

Followed by refreshments in the WTB Atrium

 

 

ALL WELCOME

 

 

 

Olivier Pourquie is Professor in the Department of Genetics at Harvard Medical School and Professor of Pathology at the Brigham and Women’s Hospital. He was the director of the Institute for Genetics and Molecular and Cellular Biology (IGBMC) in France and before that a Howard Hughes Medical Institute Investigator at the Stowers Institute for Medical Research in Kansas City. He graduated as an engineer in France and trained with Nicole Le Douarin. 
 
Dr. Pourquie authored more than 100 peer-reviewed publications. He is an elected member of the European Molecular Biology Organization and of the Academia Europea. His work on the segmentation clock that controls the periodicity of vertebrae was recognized as one of the milestones in developmental biology of the 20th century by Nature Magazine.

 

Abstract

Skeletal muscles of the body arise from segmented embryonic structures called somites. The segmental or metameric organization of somites is established early in embryogenesis when pairs of embryonic segments are rhythmically produced by the presomitic mesoderm (PSM). The tempo of somite formation is controlled by a molecular oscillator known as the segmentation clock. While this oscillator has been well characterized in model organisms, whether a similar oscillator exists in humans remains unknown. We have previously shown that human embryonic stem (ES) cells or induced pluripotent stem (iPS) cells can differentiate in vitro into PSM upon activation of the Wnt signaling pathway combined with BMP inhibition. We show that these human PSM cells exhibit Notch and YAP-dependent oscillations of the cyclic gene HES7 with a 5-hour period. Single cell RNA-sequencing comparison of the differentiating iPS cells with mouse PSM reveals that human PSM cells follow a similar differentiation path and exhibit a remarkably coordinated differentiation sequence. When these PSM-like cells are allowed to develop further in vitro, they produce striated, millimeter-long muscle fibers together with satellite-like cells. I will present the cellular and molecular characterization and the regenerative potential of these human PAX7+ satellite-like cells produced in vitro. We have also used human isogenic iPS lines differentiated to a myogenic fate to establish an in vitro model of Duchenne Muscular Dystrophy recapitulating several key features of this pathology.