TY - JOUR AB - Pancreatic islets play an essential role in regulating blood glucose level. Although the molecular pathways underlying islet cell differentiation are beginning to be resolved, the cellular basis of islet morphogenesis and fate allocation remain unclear. By combining unbiased and targeted lineage tracing, we address the events leading to islet formation in the mouse. From the statistical analysis of clones induced at multiple embryonic timepoints, here we show that, during the secondary transition, islet formation involves the aggregation of multiple equipotent endocrine progenitors that transition from a phase of stochastic amplification by cell division into a phase of sublineage restriction and limited islet fission. Together, these results explain quantitatively the heterogeneous size distribution and degree of polyclonality of maturing islets, as well as dispersion of progenitors within and between islets. Further, our results show that, during the secondary transition, α- and β-cells are generated in a contemporary manner. Together, these findings provide insight into the cellular basis of islet development. AU - Sznurkowska, Magdalena K. AU - Hannezo, Edouard B AU - Azzarelli, Roberta AU - Chatzeli, Lemonia AU - Ikeda, Tatsuro AU - Yoshida, Shosei AU - Philpott, Anna AU - Simons, Benjamin D ID - 8669 JF - Nature Communications TI - Tracing the cellular basis of islet specification in mouse pancreas VL - 11 ER - TY - JOUR AB - Cell fate transitions are key to development and homeostasis. It is thus essential to understand the cellular mechanisms controlling fate transitions. Cell division has been implicated in fate decisions in many stem cell types, including neuronal and epithelial progenitors. In other stem cells, such as embryonic stem (ES) cells, the role of division remains unclear. Here, we show that exit from naive pluripotency in mouse ES cells generally occurs after a division. We further show that exit timing is strongly correlated between sister cells, which remain connected by cytoplasmic bridges long after division, and that bridge abscission progressively accelerates as cells exit naive pluripotency. Finally, interfering with abscission impairs naive pluripotency exit, and artificially inducing abscission accelerates it. Altogether, our data indicate that a switch in the division machinery leading to faster abscission regulates pluripotency exit. Our study identifies abscission as a key cellular process coupling cell division to fate transitions. AU - Chaigne, Agathe AU - Labouesse, Céline AU - White, Ian J. AU - Agnew, Meghan AU - Hannezo, Edouard B AU - Chalut, Kevin J. AU - Paluch, Ewa K. ID - 8672 IS - 2 JF - Developmental Cell SN - 15345807 TI - Abscission couples cell division to embryonic stem cell fate VL - 55 ER - TY - JOUR AB - In the computation of the material properties of random alloys, the method of 'special quasirandom structures' attempts to approximate the properties of the alloy on a finite volume with higher accuracy by replicating certain statistics of the random atomic lattice in the finite volume as accurately as possible. In the present work, we provide a rigorous justification for a variant of this method in the framework of the Thomas–Fermi–von Weizsäcker (TFW) model. Our approach is based on a recent analysis of a related variance reduction method in stochastic homogenization of linear elliptic PDEs and the locality properties of the TFW model. Concerning the latter, we extend an exponential locality result by Nazar and Ortner to include point charges, a result that may be of independent interest. AU - Fischer, Julian L AU - Kniely, Michael ID - 8697 IS - 11 JF - Nonlinearity SN - 09517715 TI - Variance reduction for effective energies of random lattices in the Thomas-Fermi-von Weizsäcker model VL - 33 ER - TY - JOUR AB - Animal development entails the organization of specific cell types in space and time, and spatial patterns must form in a robust manner. In the zebrafish spinal cord, neural progenitors form stereotypic patterns despite noisy morphogen signaling and large-scale cellular rearrangements during morphogenesis and growth. By directly measuring adhesion forces and preferences for three types of endogenous neural progenitors, we provide evidence for the differential adhesion model in which differences in intercellular adhesion mediate cell sorting. Cell type–specific combinatorial expression of different classes of cadherins (N-cadherin, cadherin 11, and protocadherin 19) results in homotypic preference ex vivo and patterning robustness in vivo. Furthermore, the differential adhesion code is regulated by the sonic hedgehog morphogen gradient. We propose that robust patterning during tissue morphogenesis results from interplay between adhesion-based self-organization and morphogen-directed patterning. AU - Tsai, Tony Y.-C. AU - Sikora, Mateusz K AU - Xia, Peng AU - Colak-Champollion, Tugba AU - Knaut, Holger AU - Heisenberg, Carl-Philipp J AU - Megason, Sean G. ID - 8680 IS - 6512 JF - Science KW - Multidisciplinary SN - 0036-8075 TI - An adhesion code ensures robust pattern formation during tissue morphogenesis VL - 370 ER - TY - JOUR AB - Dynamic changes in the three-dimensional (3D) organization of chromatin are associated with central biological processes, such as transcription, replication and development. Therefore, the comprehensive identification and quantification of these changes is fundamental to understanding of evolutionary and regulatory mechanisms. Here, we present Comparison of Hi-C Experiments using Structural Similarity (CHESS), an algorithm for the comparison of chromatin contact maps and automatic differential feature extraction. We demonstrate the robustness of CHESS to experimental variability and showcase its biological applications on (1) interspecies comparisons of syntenic regions in human and mouse models; (2) intraspecies identification of conformational changes in Zelda-depleted Drosophila embryos; (3) patient-specific aberrant chromatin conformation in a diffuse large B-cell lymphoma sample; and (4) the systematic identification of chromatin contact differences in high-resolution Capture-C data. In summary, CHESS is a computationally efficient method for the comparison and classification of changes in chromatin contact data. AU - Galan, Silvia AU - Machnik, Nick N AU - Kruse, Kai AU - Díaz, Noelia AU - Marti-Renom, Marc A AU - Vaquerizas, Juan M ID - 8707 JF - Nature Genetics SN - 10614036 TI - CHESS enables quantitative comparison of chromatin contact data and automatic feature extraction VL - 52 ER -