title: Stochasticity and Spatial Interaction Govern Stem Cell Differentiation Dynamics.
abstract: Stem cell differentiation underlies many fundamental processes such as development, tissue growth and regeneration, as well as disease progression. Understanding how stem cell differentiation is controlled in mixed cell populations is an important step in developing quantitative models of cell population dynamics. Here we focus on quantifying the role of cell-cell interactions in determining stem cell fate. Toward this, we monitor stem cell differentiation in adherent cultures on micropatterns and collect statistical cell fate data. Results show high cell fate variability and a bimodal probability distribution of stem cell fraction on small (80-140 μm diameter) micropatterns. On larger (225-500 μm diameter) micropatterns, the variability is also high but the distribution of the stem cell fraction becomes unimodal. Using a stochastic model, we analyze the differentiation dynamics and quantitatively determine the differentiation probability as a function of stem cell fraction. Results indicate that stem cells can interact and sense cellular composition in their immediate neighborhood and adjust their differentiation probability accordingly. Blocking epithelial cadherin (E-cadherin) can diminish this cell-cell contact mediated sensing. For larger micropatterns, cell motility adds a spatial dimension to the picture. Taken together, we find stochasticity and cell-cell interactions are important factors in determining cell fate in mixed cell populations.
authors.affiliation: Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218.
authors.forename: Quinton
authors.initials: Q
authors.lastname: Smith
authors.affiliation: 1] Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD 21218. [2] Johns Hopkins Physical Sciences-Oncology Center, Johns Hopkins University, Baltimore, MD 21218.
authors.forename: Evgeny
authors.initials: E
authors.lastname: Stukalin
authors.affiliation: 1] Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218. [2] Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218.
authors.forename: Sravanti
authors.initials: S
authors.lastname: Kusuma
authors.affiliation: 1] Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218. [2] Johns Hopkins Physical Sciences-Oncology Center, Johns Hopkins University, Baltimore, MD 21218. [3] Department of Material Science and Engineering, Johns Hopkins University, Baltimore, MD 21218.
authors.forename: Sharon
authors.initials: S
authors.lastname: Gerecht
authors.affiliation: 1] Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD 21218. [2] Johns Hopkins Physical Sciences-Oncology Center, Johns Hopkins University, Baltimore, MD 21218. [3] Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218.
authors.forename: Sean X
authors.initials: SX
authors.lastname: Sun
mesh_terms: D015820:Cadherins / Q000378:metabolism; D002450:Cell Communication; D002454:Cell Differentiation / Q000502:physiology*; D002465:Cell Movement; D002478:Cells, Cultured; D006801:Humans; D008954:Models, Biological; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D013269:Stochastic Processes
chemical_list: D015820:Cadherins