Live Visualization of ERK Activity in the Mouse Blastocyst Reveals Lineage-Specific Signaling Dynamics

For the past twenty five years the NIH family of imaging software, NIH Image and ImageJ have been pioneers as open tools for scientific image analysis. We discuss the origins, challenges and solutions of these two programs, and how their history can serve to advise and inform other software projects.

In the three decades since pluripotent mouse embryonic stem (ES) cells were first described they have been derived and maintained by using various empirical combinations of feeder cells, conditioned media, cytokines, growth factors, hormones, fetal calf serum, and serum extracts. Consequently ES-cell self-renewal is generally considered to be dependent on multifactorial stimulation of dedicated transcriptional circuitries, pre-eminent among which is the activation of STAT3 by cytokines (ref. 8). Here we show, however, that extrinsic stimuli are dispensable for the derivation, propagation and pluripotency of ES cells. Self-renewal is enabled by the elimination of differentiation-inducing signalling from mitogen-activated protein kinase. Additional inhibition of glycogen synthase kinase 3 consolidates biosynthetic capacity and suppresses residual differentiation. Complete bypass of cytokine signalling is confirmed by isolating ES cells genetically devoid of STAT3. These findings reveal that ES cells have an innate programme for self-replication that does not require extrinsic instruction. This property may account for their latent tumorigenicity. The delineation of minimal requirements for self-renewal now provides a defined platform for the precise description and dissection of the pluripotent state.

A growing number of studies are revealing that cells can send and receive information by controlling the temporal behavior (dynamics) of their signaling molecules. In this Review, we discuss what is known about the dynamics of various signaling networks and their role in controlling cellular responses. We identify general principles that are emerging in the field, focusing specifically on how the identity and quantity of a stimulus is encoded in temporal patterns, how signaling dynamics influence cellular outcomes, and how specific dynamical patterns are both shaped and interpreted by the structure of molecular networks. We conclude by discussing potential functional roles for transmitting cellular information through the dynamics of signaling molecules and possible applications for the treatment of disease. Copyright © 2013 Elsevier Inc. All rights reserved.