Engineering mouse cell fate controller by rational design.

Cell fate is likely regulated by a common machinery, while components of this machine remain to be identified. Here we report the design and testing of engineered cell fate controller NanogBiD, fusing BiD or BRG1 interacting domain of SS18 with Nanog. NanogBiD promotes mouse somatic cell reprogramming efficiently in contrast to the ineffective native protein under multiple testing conditions. Mechanistic studies further reveal that it facilitates cell fate transition by recruiting the intended Brg/Brahma-associated factor (BAF) complex to modulate chromatin accessibility and reorganize cell state specific enhancers known to be occupied by canonical Nanog, resulting in precocious activation of multiple genes including Sall4, miR-302, Dppa5a and Sox15 towards pluripotency. Although we have yet to test our approach in other species, our findings suggest that engineered chromatin regulators may provide much needed tools to engineer cell fate in the cells as drugs era.

Exclusion of HDAC1/2 complexes by oncogenic nuclear condensates.

Nuclear condensates have been shown to regulate cell fate control, but its role in oncogenic transformation remains largely unknown. Here we show acquisition of oncogenic potential by nuclear condensate remodeling. The proto-oncogene SS18 and its oncogenic fusion SS18-SSX1 can both form condensates, but with drastically different properties and impact on 3D genome architecture. The oncogenic condensates, not wild type ones, readily exclude HDAC1 and 2 complexes, thus, allowing aberrant accumulation of H3K27ac on chromatin loci, leading to oncogenic expression of key target genes. These results provide the first case for condensate remodeling as a transforming event to generate oncogene and such condensates can be targeted for therapy. One sentence summary: Expulsion of HDACs complexes leads to oncogenic transformation.

Representation of the spatio-temporal narrative of The Tale of Li Wa.

This paper posits a framework of digital models integrating spatial narrative theories to represent the narrative and its experience of a Chinese classical novel, The Tale of Li Wa, which has been diversely interpreted by literary critics and historians for approximately 900 years. In the proposed framework of "Time-Space-time-Space," the spatio-temporal information derived from the text of the novel and its author is extracted and fused to map the instantaneous spatial pattern perceived by readers in the flow of read time, which helps contemporary readers re-understand the classical narrative and its context through a multi-possibilities, integrated, and in-depth approach. The paper presents one possible interpretation of the novel in the framework organized by the authors, illustrating the theme of growth with respect to the male protagonist in the capital Chang'an via the "what-how-why" model.