Cell-of-Origin-Specific 3D Genome Structure Acquired during Somatic Cell Reprogramming

Area of Science:

• Cell biology
• Genomics
• Epigenetics

Background:

• Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) using specific factors.
• Cellular reprogramming involves significant changes in gene expression and epigenetic states.
• The three-dimensional (3D) genome organization, including topologically associated domains (TADs), plays a crucial role in cellular identity.

Purpose of the Study:

• To investigate the dynamics of genome topology during the reprogramming of various somatic cell types into iPSCs.
• To understand how somatic cell-specific 3D genome structures are altered and how embryonic stem cell (ESC)-like topologies are established.
• To determine if iPSCs retain any topological memory of their somatic cell of origin.

Main Methods:

• Analysis of genome topology using techniques like Hi-C.
• Comparison of 3D genome conformations across different somatic cell types and their corresponding iPSCs.
• Investigating the acquisition of new topological features during the reprogramming process.

Main Results:

• Reprogramming induces large-scale repositioning of topologically associated domains (TADs).
• Somatic cell-specific genomic neighborhoods and chromatin loops are dismantled, replaced by ESC-like 3D genome structures.
• Early passage iPSCs exhibit distinct topological features that correlate with their cell of origin.
• These distinguishing topological hallmarks are acquired during reprogramming, not inherited from somatic cell topology.

Conclusions:

• Cellular reprogramming fundamentally remodels the 3D genome architecture, erasing somatic cell identity.
• iPSCs acquire unique topological signatures during reprogramming that reflect their cell of origin.
• These findings highlight the plasticity of genome topology and its role in maintaining cellular identity and memory.