Dynamics of lineage commitment revealed by single-cell transcriptomics of differentiating embryonic stem cells

Stefan Semrau, Johanna E Goldmann, Magali Soumillon, Tarjei S Mikkelsen, Rudolf Jaenisch, Alexander van Oudenaarden

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgaveArtikelWetenschappelijkpeer review

Samenvatting

Gene expression heterogeneity in the pluripotent state of mouse embryonic stem cells (mESCs) has been increasingly well-characterized. In contrast, exit from pluripotency and lineage commitment have not been studied systematically at the single-cell level. Here we measure the gene expression dynamics of retinoic acid driven mESC differentiation from pluripotency to lineage commitment, using an unbiased single-cell transcriptomics approach. We find that the exit from pluripotency marks the start of a lineage transition as well as a transient phase of increased susceptibility to lineage specifying signals. Our study reveals several transcriptional signatures of this phase, including a sharp increase of gene expression variability and sequential expression of two classes of transcriptional regulators. In summary, we provide a comprehensive analysis of the exit from pluripotency and lineage commitment at the single cell level, a potential stepping stone to improved lineage manipulation through timing of differentiation cues.

Originele taal-2Engels
Pagina's (van-tot)1096
TijdschriftNature Communications
Volume8
Nummer van het tijdschrift1
DOI's
StatusGepubliceerd - 23 okt 2017

Vingerafdruk

Duik in de onderzoeksthema's van 'Dynamics of lineage commitment revealed by single-cell transcriptomics of differentiating embryonic stem cells'. Samen vormen ze een unieke vingerafdruk.

Citeer dit