Sadeghi, M. — Page 3 | bioRxiv Science

bioRxiv2017

Noise-driven Cell Differentiation and the Emergence of Organization

One of the major transitions in evolution is the step from unicellularity into the brave new world of multicellularity. To understand this feat, one has to fathom two main characteristics of multicellular organisms: differentiation and self-organization. Any explanation concerning this major transition should involve mechanisms that can simultaneously explain the marvellous intricacies manifest in the aforementioned characteristics, and an account of the evolution of such traits. Here we propose a noise-driven differentiation (NDD) model. The reliance on noise, in place of a more mechanistic approach, makes the NDD model a more suitable approach to explain differentiation and self-organization. Furthermore, our model sheds some light on the possible evolutionary origins of these biological innovations. To test the NDD model, we utilize a model of cell aggregation. The behavior of this model of cell aggregation is in concert with the NDD model.

cell biology↗

bioRxiv2017

Elucidation of the 14-3-3ζ interactome reveals critical roles of RNA splicing factors during adipogenesis

Adipogenesis is facilitated by a complex signaling network requiring strict temporal and spatial organization of effector molecules. Molecular scaffolds, such as 14-3-3 proteins, coordinate such events, and we have previously identified 14-3-3{zeta} as an essential scaffold in adipocyte differentiation. The interactome of 14-3-3{zeta} is large and diverse, and it is possible that novel adipogenic factors may be present within it. Mouse embryonic fibroblasts from mice over-expressing a TAP-epitope-tagged 14-3-3{zeta} molecule were generated, and following the induction of adipogenesis, TAP-14-3-3{zeta} complexes were purified, followed by mass spectrometry analysis to determine the 14-3-3{zeta} interactome. Over 100 proteins were identified as being unique to adipocyte differentiation, of which 56 were novel interacting partners. Previously established regulators of adipogenesis (ie, Ptrf/Cavin1 and Phb2) were found within the 14-3-3{zeta} interactome, confirming the ability of this approach to identify regulators of adipocyte differentiation. An enrichment of proteins in the interactome related to RNA metabolism, processing, and splicing was identified, and analysis of transcriptomic data revealed that 14-3-3{zeta} depletion in 3T3-L1 cells affected the alternative splicing of mRNA during adipocyte differentiation. Of the RNA splicing factors within the 14-3-3{zeta} interactome, depletion of Hnrnpf, Hnrnpk, Ddx6, and Sfpq by siRNA revealed essential roles of these proteins in adipogenesis and their roles in the alternative splicing of Lpin1. In summary, novel adipogenic factors can be detected within the 14-3-3{zeta} interactome, and further characterization of additional proteins within the 14-3-3{zeta} interactome has the potential of identifying novel targets to block the expansion of adipose tissue mass that occurs in obesity.

physiology↗