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Updated: Jul 29, 2025

Isolation of Nuclei from Flash-Frozen Liver Tissue for Single-Cell Multiomics

Isolation of Nuclei from Flash-Frozen Liver Tissue for Single-Cell Multiomics

Published on: December 9, 2022

High-resolution spatial multi-omics reveals cell-type specific nuclear compartments.

Yodai Takei¹, Yujing Yang¹, Jonathan White¹

¹Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.

Biorxiv : the Preprint Server for Biology

|May 22, 2023

Summary

This summary is machine-generated.

This study reveals how cell-type specific nuclear structures organize the genome in single cells. It maps DNA, RNA, and protein structures to understand gene regulation and 3D genome organization.

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Last Updated: Jul 29, 2025

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Author Spotlight: Advancing Biomedical Research Through Single Cell Analysis

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Author Spotlight: Nuclei Isolation from Mouse Cardiac Progenitor Cells for Epigenome and Gene Expression Profiling at Single-Cell Resolution

Author Spotlight: Nuclei Isolation from Mouse Cardiac Progenitor Cells for Epigenome and Gene Expression Profiling at Single-Cell Resolution

Published on: May 12, 2023

Area of Science:

Cell Biology
Genomics
Epigenetics

Background:

The mammalian nucleus is organized by diverse, cell-type specific subnuclear structures.
These structures, involving nuclear bodies and histone modifications, influence gene regulation and 3D genome organization.
Understanding nuclear organization requires mapping molecular constituents to genomic loci in single cells within tissues.

Purpose of the Study:

To introduce a novel multi-omics method for high-resolution single-cell analysis of nuclear organization.
To map genomic loci, nascent transcriptome, and subnuclear structures simultaneously in individual cells.
To investigate cell-type specific variations in chromatin compartments and their relationship with gene regulation.

Main Methods:

Developed two-layer DNA seqFISH+ for simultaneous mapping of 100,049 genomic loci, 17,856 nascent transcripts, and immunofluorescently labeled subnuclear structures.
Applied the method to cell lines and adult mouse cerebellum, analyzing multi-omics data from single cells.
Utilized computational analysis to correlate subnuclear structures with genomic features and gene expression patterns.

Main Results:

Repressive chromatin compartments exhibit greater cell-type variability than active compartments.
An RNA polymerase II (RNAPII)-enriched compartment was linked to long, cell-type specific genes, distinct from nuclear speckles.
Cell-type specific heterochromatin (H3K27me3, H4K20me3) compartments influence radial positioning and inter-chromosomal interactions in neurons and glial cells.

Conclusions:

Provides a high-resolution, single-cell multi-omics view of subnuclear compartments and their associated genomic loci.
Demonstrates the impact of subnuclear structures on gene regulation and 3D genome organization within complex tissues.
Highlights the cell-type specificity of nuclear organization and its role in neuronal and glial cell function.