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Genomic DNA in Eukaryotes

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Related Experiment Video

Updated: May 11, 2026

Cell Lineage Analyses and Gene Function Studies Using Twin-spot MARCM
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Multimodal cell maps as a foundation for structural and functional genomics.

Leah V Schaffer1, Mengzhou Hu1, Gege Qian1,2

  • 1Department of Medicine, University of California San Diego, La Jolla, CA, USA.

Nature
|April 9, 2025
PubMed
Summary
This summary is machine-generated.

Scientists mapped human cell architecture by analyzing protein interactions and images. This revealed 275 molecular assemblies, new protein functions, and insights into pediatric cancer genomes.

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Area of Science:

  • Cellular Biology
  • Structural Biology
  • Genomics

Background:

  • Human cells possess a complex, largely unexplored subcellular architecture.
  • Understanding this organization is crucial for deciphering cellular functions and disease mechanisms.

Purpose of the Study:

  • To create a comprehensive map of human subcellular architecture.
  • To identify and characterize molecular assemblies and their functions.
  • To explore the implications of this map for structural biology and cancer genomics.

Main Methods:

  • Joint measurement of biophysical interactions and immunofluorescence imaging for over 5,100 proteins in U2OS cells.
  • Self-supervised multimodal data integration to resolve molecular assemblies.
  • Systematic validation using whole-cell size-exclusion chromatography and annotation with large language models.

Main Results:

  • Resolved 275 molecular assemblies across a range of 10^-8 to 10^-5 m.
  • Determined structures for 111 heterodimeric complexes and an expanded Rag-Ragulator assembly.
  • Assigned novel functions to 975 proteins, identified cell-type specific assemblies, and implicated 102 new cancer proteins by analyzing pediatric cancer genomes.

Conclusions:

  • The global map provides a foundational resource for structural and functional cell biology.
  • This work advances our understanding of cellular organization and its role in health and disease.
  • The Cell Visualization Portal and Mapping Toolkit offer a valuable platform for future research.