Instytut Podstawowych Problemów Techniki
Polskiej Akademii Nauk

Partnerzy

Chengzhe Tian

University of Copenhagen (DK)

Ostatnie publikacje
1.  Kellogg R.A., Tian C., Lipniacki T., Quake S.R., Tay S., Digital signaling decouples activation probability and population heterogeneity, eLife, ISSN: 2050-084X, DOI: 10.7554/eLife.08931, Vol.4, pp.e08931-1-26, 2015

Streszczenie:
Digital signaling enhances robustness of cellular decisions in noisy environments, but it is unclear how digital systems transmit temporal information about a stimulus. To understand how temporal input information is encoded and decoded by the NF-κB system, we studied transcription factor dynamics and gene regulation under dose- and duration-modulated inflammatory inputs. Mathematical modeling predicted and microfluidic single-cell experiments confirmed that integral of the stimulus (or area, concentration × duration) controls the fraction of cells that activate NF-κB in the population. However, stimulus temporal profile determined NF-κB dynamics, cell-to-cell variability, and gene expression phenotype. A sustained, weak stimulation lead to heterogeneous activation and delayed timing that is transmitted to gene expression. In contrast, a transient, strong stimulus with the same area caused rapid and uniform dynamics. These results show that digital NF-κB signaling enables multidimensional control of cellular phenotype via input profile, allowing parallel and independent control of single-cell activation probability and population heterogeneity.

Afiliacje autorów:
Kellogg R.A. - Eidgenössische Technische Hochschule Zürich (CH)
Tian C. - University of Copenhagen (DK)
Lipniacki T. - IPPT PAN
Quake S.R. - Stanford University (US)
Tay S. - Eidgenössische Technische Hochschule Zürich (CH)
45p.

Kategoria A Plus

IPPT PAN

logo ippt            ul. Pawińskiego 5B, 02-106 Warszawa
  +48 22 826 12 81 (centrala)
  +48 22 826 98 15
 

Znajdź nas

mapka
© Instytut Podstawowych Problemów Techniki Polskiej Akademii Nauk 2024