Repository logo
 

Mapping the route from naive pluripotency to lineage specification.


Type

Article

Change log

Authors

Kalkan, Tüzer 

Abstract

In the mouse blastocyst, epiblast cells are newly formed shortly before implantation. They possess a unique developmental plasticity, termed naive pluripotency. For development to proceed, this naive state must be subsumed by multi-lineage differentiation within 72 h following implantation. In vitro differentiation of naive embryonic stem cells (ESCs) cultured in controlled conditions provides a tractable system to dissect and understand the process of exit from naive pluripotency and entry into lineage specification. Exploitation of this system in recent large-scale RNAi and mutagenesis screens has uncovered multiple new factors and modules that drive or facilitate progression out of the naive state. Notably, these studies show that the transcription factor network that governs the naive state is rapidly dismantled prior to upregulation of lineage specification markers, creating an intermediate state that we term formative pluripotency. Here, we summarize these findings and propose a road map for state transitions in ESC differentiation that reflects the orderly dynamics of epiblast progression in the embryo.

Description

Keywords

embryonic stem cells, epiblast, lineage specification, pluripotency, self-renewal, signalling, Animals, Cell Differentiation, Cell Lineage, Gene Expression Regulation, Developmental, Genes, Reporter, Germ Layers, Mice, Models, Biological, Pluripotent Stem Cells, Transcription Factors

Journal Title

Philos Trans R Soc Lond B Biol Sci

Conference Name

Journal ISSN

0962-8436
1471-2970

Volume Title

370

Publisher

The Royal Society
Sponsorship
Research in the laboratory is funded by the Wellcome Trust, the Biotechnology and Biological Sciences Research Council and the European Commission.