title: Studying lineage decision-making in vitro: emerging concepts and novel tools.
abstract: Correct and timely lineage decisions are critical for normal embryonic development and homeostasis of adult tissues. Therefore, the search for fundamental principles that underlie lineage decision-making lies at the heart of developmental biology. Here, we review attempts to understand lineage decision-making as the interplay of single-cell heterogeneity and gene regulation. Fluctuations at the single-cell level are an important driving force behind cell-state transitions and the creation of cell-type diversity. Gene regulatory networks amplify such fluctuations and define stable cell types. They also mediate the influence of signaling inputs on the lineage decision. In this review, we focus on insights gleaned from in vitro differentiation of embryonic stem cells. We discuss emerging concepts, with an emphasis on transcriptional regulation, dynamical aspects of differentiation, and functional single-cell heterogeneity. We also highlight some novel tools to study lineage decision-making in vitro.
authors.affiliation: Leiden University, 2333 CC Leiden, The Netherlands; email: semrau@physics.leidenuniv.nl.
authors.forename: Stefan
authors.initials: S
authors.lastname: Semrau
authors.forename: Alexander
authors.initials: A
authors.lastname: van Oudenaarden
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics*; D047108:Embryonic Development / Q000235:genetics; D053595:Embryonic Stem Cells / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D053263:Gene Regulatory Networks / Q000235:genetics*; D006801:Humans; D015398:Signal Transduction / Q000235:genetics
keywords: embryonic stem cells; gene regulatory networks; in vitro differentiation; lineage decision-making; single-cell heterogeneity