Cell population dynamics model for deconvolution of murine embryonic stem cell self-renewal and differentiation responses to cytokines and extracellular matrix.
Stem cell self-renewal versus differentiation fate decisions are difficult to characterize and analyze due to multiple competing rate processes occurring simultaneously among heterogeneous cell subpopulations. To address this challenge, we describe a mathematical model for cell population dynamics that allows flow cytometry measurement of population distributions of molecular markers to be deconvoluted in terms of subpopulation-specific rate parameters distinguishing commitment to differentiation, proliferation of differentiated cells, and proliferation of undifferentiated cells (i.e., self-renewal). We validate this model-based parameter determination by means of dedicated, independent cell-tracking studies. Our approach facilitates interpretation of relationships underlying effects of external cues on cell responses in differentiating cultures via intracellular signals.
Department of Chemical Engineering, Massachusetts Institute of Technology, 25 Ames Street, 56-341, Cambridge, Massachusetts 02139, USA.
Wendy A
WA
Prudhomme
Keith H
KH
Duggar
Douglas A
DA
Lauffenburger
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000528:radiation effects; D002469:Cell Separation / Q000379:methods*; D002478:Cells, Cultured; D003198:Computer Simulation; D016207:Cytokines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D016326:Extracellular Matrix Proteins / Q000494:pharmacology*; D005434:Flow Cytometry / Q000379:methods*; D051379:Mice; D008954:Models, Biological; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*
D016207:Cytokines; D016326:Extracellular Matrix Proteins