Reusing and composing models of cell fate regulation of human bone precursor cells.
In order to treat osteoporosis and other bone mass disorders it is necessary to understand the regulatory processes that control the cell fate decisions responsible for going from bone precursor cells to bone tissue. Many processes interact to regulate cell division, differentiation and apoptosis. There are models for these basic processes, but not for their interactions. In this work we use the theory of switched systems, reuse and composition of validated models to describe the cell fate decisions leading to bone and fat formation. We describe the differentiation of osteo-adipo progenitor cells by composing its model with differentiation stimuli. We use the activation of the Wnt pathway as stimulus to osteoblast lineage, including regulation of cell division and apoptosis. This model is our first step to simulate physiological responses in silico to treatments for bone mass disorders.
INRIA Bordeaux Sud-Ouest, Project-team (EPC) MAGNOME common to INRIA, CNRS, Talence, France. rodrigo.assar@gmail.com
Rodrigo
R
Assar
Andrea V
AV
Leisewitz
Alice
A
Garcia
Nibaldo C
NC
Inestrosa
Martín A
MA
Montecino
David J
DJ
Sherman
D017667:Adipocytes / Q000166:cytology / Q000502:physiology; D050156:Adipogenesis; D017209:Apoptosis; D002454:Cell Differentiation; D002455:Cell Division; D019070:Cell Lineage; D020219:Chondrogenesis; D005260:Female; D053263:Gene Regulatory Networks; D006801:Humans; D008297:Male; D008954:Models, Biological; D010006:Osteoblasts / Q000166:cytology* / Q000502:physiology*; D010012:Osteogenesis; D010024:Osteoporosis / Q000473:pathology / Q000628:therapy; D049490:Systems Biology; D060449:Wnt Signaling Pathway