biostudies-literatureUnknown6Boxman JEmbryonic stem cells can spontaneously differentiate into cell types of all germ layers within embryoid bodies (EBs) in a highly variable manner. Whether there exists an intrinsic differentiation program common to all EBs is unknown. Here, we present a novel combination of high-throughput live two-photon imaging and gene expression profiling to study early differentiation dynamics spontaneously occurring within developing EBs. Onset timing of Brachyury-GFP was highly variable across EBs, while the spatial patterns as well as the dynamics of mesendodermal progression following onset were remarkably similar. We therefore defined a 'developmental clock' using the Brachyury-GFP signal onset timing. Mapping snapshot gene expression measurements to this clock revealed their temporal trends, indiScientific reports31623https://www.ebi.ac.uk/biostudies/studies/S-EPMC4987683biostudies-literatureIntegrated live imaging and molecular profiling of embryoid bodies reveals a synchronized progression of early differentiation.PMC4987683Vadigepalli RNachman IAchanta SSagy NBoxman JfalseIntegrated live imaging and molecular profiling of embryoid bodies reveals a synchronized progression of early differentiation.Embryonic stem cells can spontaneously differentiate into cell types of all germ layers within embryoid bodies (EBs) in a highly variable manner. Whether there exists an intrinsic differentiation program common to all EBs is unknown. Here, we present a novel combination of high-throughput live two-photon imaging and gene expression profiling to study early differentiation dynamics spontaneously occurring within developing EBs. Onset timing of Brachyury-GFP was highly variable across EBs, while the spatial patterns as well as the dynamics of mesendodermal progression following onset were remarkably similar. We therefore defined a 'developmental clock' using the Brachyury-GFP signal onset timing. Mapping snapshot gene expression measurements to this clock revealed their temporal trends, indi2016-01-01T00:00:00Z2016 Aug2025-04-04T10:35:58.851Z2019-03-27T02:20:50ZS-EPMC49876832753059910.1038/srep31623