Nuclear receptor-SINE B1 network modulates expanded pluripotency in blastoids and blastocysts
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View abstract on PubMed
Summary
This summary is machine-generated.Scientists discovered an intrinsic program, driven by nuclear receptor subfamily 1, group H, member 2 (Nr1h2), that is crucial for blastoid and early embryo development. Nr1h2 rewires stem cells, enhancing blastoid formation and in vivo contribution.
Area Of Science
- Developmental Biology
- Stem Cell Biology
- Genetics
Background
- Embryonic stem cells (ESCs) can self-organize into blastocyst-like structures (blastoids).
- Blastoids are valuable models for studying early embryogenesis.
- Intrinsic regulators of blastoid formation are largely unknown.
Purpose Of The Study
- To identify intrinsic regulators governing blastoid formation.
- To understand the role of these regulators in early embryonic development.
- To characterize the molecular mechanisms underlying blastoid development.
Main Methods
- Development of metrics to grade blastoid resemblance to mouse blastocysts.
- Analysis of differential gene regulon activation in blastoids.
- Functional studies involving abrogation and activation of specific genes (Nr1h2).
- Integrative multi-omics analyses (transcriptome, epigenome, chromatin accessibility).
Main Results
- Identified an intrinsic program crucial for blastoids and blastocysts across species.
- Nuclear receptor subfamily 1, group H, member 2 (Nr1h2) is essential for blastoid formation.
- Nr1h2 activation induces a unique pluripotency state in ESCs, promoting blastoid formation with enhanced in vivo implantation and lineage contribution.
- Nr1h2 regulates genes involved in embryonic lineage specification and SINE-B1 transposable elements.
Conclusions
- Nr1h2 is a key intrinsic regulator of blastoid and early embryo development.
- The Nr1h2-centered program governs lineage specification and developmental potential.
- This study provides insights into the fundamental mechanisms of early embryogenesis using stem cell-based models.
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