Studying Lineage Decision-Making In Vitro: Emerging Concepts and Novel Tools

TY - JOUR

T1 - Studying Lineage Decision-Making In Vitro

T2 - Emerging Concepts and Novel Tools

AU - Semrau, Stefan

AU - van Oudenaarden, Alexander

PY - 2015/11/13

Y1 - 2015/11/13

N2 - 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.

AB - 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.

U2 - 10.1146/annurev-cellbio-100814-125300

DO - 10.1146/annurev-cellbio-100814-125300

M3 - Article

C2 - 26566114

SN - 1081-0706

VL - 31

SP - 317

EP - 345

JO - Annual Review of Cell and Developmental Biology

JF - Annual Review of Cell and Developmental Biology

ER -