Proliferation tracing with single-cell mass cytometry optimizes generation of stem cell memory-like T cells.

Selective differentiation of naive T cells into multipotent T cells is of great interest clinically for the generation of cell-based cancer immunotherapies. Cellular differentiation depends crucially on division state and time. Here we adapt a dye dilution assay for tracking cell proliferative history through mass cytometry and uncouple division, time and regulatory protein expression in single naive human T cells during their activation and expansion in a complex ex vivo milieu. Using 23 markers, we defined groups of proteins controlled predominantly by division state or time and found that undivided cells account for the majority of phenotypic diversity. We next built a map of cell state changes during naive T-cell expansion. By examining cell signaling on this map, we rationally selected ibrutinib, a BTK and ITK inhibitor, and administered it before T cell activation to direct differentiation toward a T stem cell memory (TSCM)-like phenotype. This method for tracing cell fate across division states and time can be broadly applied for directing cellular differentiation

Networking Phylogeny for Indo-European and Austronesian Languages

Harnessing cognitive abilities of many individuals, a language evolves upon their mutual interactions establishing a persistent social environment to which language is closely attuned. Human history is encoded in the rich sets of linguistic data by means of symmetry patterns that are not always feasibly represented by trees. Here we use the methods developed in the study of complex networks to decipher accurately symmetry records on the language phylogeny of the Indo-European and the Austronesian language families, considering, in both cases, the samples of fifty different languages. In particular, we support the Anatolian theory of Indo-European origin and the ‘express train’ model of Austronesian expansion from South-East Asia, with an essential role for the Batanes islands located between the Philippines and Taiwan