Single-cell 3D genome structure reveals distinct human pluripotent states

Area of Science:

• Stem cell biology
• Genomics
• Epigenetics

Background:

• Pluripotent states of embryonic stem cells (ESCs) influence differentiation capacity and therapeutic potential.
• Mechanisms regulating transcription and pluripotent states in human pluripotent stem cells (hPSCs) remain unclear.

Purpose of the Study:

• To investigate the association between 3D genomic structure and pluripotent states in hESCs.
• To elucidate the mechanisms controlling transcription and chromatin organization in naive and primed hPSCs.

Main Methods:

• Single-cell analysis of high-resolution, three-dimensional (3D) genomic structure.
• Chromatin structure and compartmentalization analysis.

Main Results:

• Naive pluripotent state exhibits specialized 3D genomic structures with clear chromatin compartmentalization, distinct from the primed state.
• Naive state involves remodeling of active euchromatin and reduced nuclear interactions, enhancing accessibility of naive pluripotent genes.
• Primed state shows intermingled genomic organization with active euchromatin at the periphery and heterochromatin at the center.

Conclusions:

• Chromatin structure remodeling is associated with hESC pluripotent states.
• Specific patterns of transcription and chromatin structure modifications define naive and primed hESCs.
• Compartmentalization of heterochromatin and euchromatin regulates chromatin accessibility and defines pluripotent states and cellular identity.