General Applicability of Synthetic Gene-Overexpression for Cell-Type Ratio Control via Reprogramming

Kana Ishimatsu, Takashi Hata, Atsushi Mochizuki, Ryoji Sekine, Masayuki Yamamura, Daisuke Kiga

Research output: Contribution to journalArticle

5 Citations (Scopus)

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. (Figure Presented).

Original languageEnglish
Pages (from-to)638-644
Number of pages7
JournalACS Synthetic Biology
Volume3
Issue number9
DOIs
Publication statusPublished - 2014 Sep 19

Keywords

  • cell-type ratio control
  • gene overexpression
  • multipotency

ASJC Scopus subject areas

  • Biomedical Engineering
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)

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