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.
Prudhomme
Wendy A
WA
Department of Chemical Engineering, Massachusetts Institute of Technology, 25 Ames Street, 56-341, Cambridge, Massachusetts 02139, USA.
Duggar
Keith H
KH
Lauffenburger
Douglas A
DA
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