Massively multiplex single-cell Hi-C

Area of Science:

• Genomics
• Molecular Biology
• Cell Biology

Background:

• Chromosome conformation capture (3C) methods provide insights into 3D genome organization.
• Existing methods often lack the resolution to capture cell-to-cell heterogeneity.
• Single-cell genomics aims to dissect biological systems at the individual cell level.

Purpose of the Study:

• To introduce single-cell combinatorial indexed Hi-C (sciHi-C), a novel method for analyzing genome-wide chromatin interactions in single cells.
• To demonstrate the feasibility and utility of sciHi-C in capturing cell-to-cell variability.
• To establish combinatorial indexing as a versatile strategy for single-cell genomic applications.

Main Methods:

• Adaptation of the Hi-C technique using combinatorial cellular indexing.
• Generation and sequencing of six sciHi-C libraries from a total of 10,696 single cells.
• Computational analysis of sciHi-C data to resolve individual cellular conformations.

Main Results:

• Successful generation of high-throughput single-cell Hi-C data.
• Identification of cell-to-cell heterogeneity in mammalian chromosomal conformation.
• Distinguishing cells based on karyotypic and cell-cycle states using sciHi-C data.

Conclusions:

• Combinatorial indexing is a powerful and generalizable strategy for single-cell genomics.
• sciHi-C enables the study of genome architecture heterogeneity at an unprecedented scale.
• This method opens new avenues for understanding cell-specific genome functions.