title: General applicability of synthetic gene-overexpression for cell-type ratio control via reprogramming.
abstract: Control of the cell-type ratio in multistable systems requires wide-range control of the initial states of cells. Here, using a synthetic circuit in E. coli, we describe the use of a simple gene-overexpression system combined with a bistable toggle switch, for the purposes of enabling the wide-range control of cellular states and thus generating arbitrary cell-type ratios. Theoretically, overexpression induction temporarily alters the bistable system to a monostable system, in which the location of the single steady state of cells can be manipulated over a wide range by regulating the overexpression levels. This induced cellular state becomes the initial state of the basal bistable system upon overexpression cessation, which restores the original bistable system. We experimentally demonstrated that the overexpression induced a monomodal cell distribution, and subsequent overexpression withdrawal generated a bimodal distribution. Furthermore, as designed theoretically, regulating the overexpression levels by adjusting the concentrations of small molecules generated arbitrary cell-type ratios.
authors.affiliation: Department of Computational Intelligence and Systems Science, Tokyo Institute of Technology , Kanagawa 226-8503, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Ishimatsu
authors.forename: Takashi
authors.initials: T
authors.lastname: Hata
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mochizuki
authors.forename: Ryoji
authors.initials: R
authors.lastname: Sekine
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamamura
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kiga
mesh_terms: D054742:Acyl-Butyrolactones / Q000494:pharmacology; D001089:Arabinose / Q000494:pharmacology; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D005813:Genes, Synthetic / Q000235:genetics*; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D054742:Acyl-Butyrolactones; D029968:Escherichia coli Proteins; D011994:Recombinant Proteins; D001089:Arabinose
keywords: cell-type ratio control; gene overexpression; multipotency