Lineage-Specific Profiling Delineates the Emergence and Progression of Naive Pluripotency in Mammalian Embryogenesis

Summary

Naive pluripotency is manifest in the preimplantation mammalian embryo. Here we determine transcriptome dynamics of mouse development from the eight-cell stage to postimplantation using lineage-specific RNA sequencing. This method combines high sensitivity and reporter-based fate assignment to acquire the full spectrum of gene expression from discrete embryonic cell types. We define expression modules indicative of developmental state and temporal regulatory patterns marking the establishment and dissolution of naive pluripotency in vivo. Analysis of embryonic stem cells and diapaused embryos reveals near-complete conservation of the core transcriptional circuitry operative in the preimplantation epiblast. Comparison to inner cell masses of marmoset primate blastocysts identifies a similar complement of pluripotency factors but use of alternative signaling pathways. Embryo culture experiments further indicate that marmoset embryos utilize WNT signaling during early lineage segregation, unlike rodents. These findings support a conserved transcription factor foundation for naive pluripotency while revealing species-specific regulatory features of lineage segregation.

Highlights

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  Transcriptome profiling establishes a reference map for early mouse development

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  Lineage-specific RNA-seq captures the full dynamic range of gene expression

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  ESCs and diapaused and preimplantation epiblasts share common pluripotency circuitry

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  Primate early ICM utilizes additional signaling pathways for lineage specification

Abstract

In this Resource article, Boroviak et al. perform lineage-specific transcriptome analysis of early mouse, diapaused, and marmoset embryos, defining regulatory modules mediating the establishment and loss of naive pluripotency. Cross-species comparisons reveal a conserved pluripotency transcriptional network but distinct signaling pathways for segregation of the inner cell mass.