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Updated: Sep 17, 2025

Generation of Integration-free Human Induced Pluripotent Stem Cells Using Hair-derived Keratinocytes
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The Somatic Mosaicism across Human Tissues Network.

Tim H H Coorens1,2, Ji Won Oh3,4, Yujin Angelina Choi5

  • 1Broad Institute of MIT and Harvard, Cambridge, MA, USA. tcoorens@broadinstitute.org.

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|July 3, 2025
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Summary
This summary is machine-generated.

This study catalogues somatic mutations in healthy human tissues to understand their patterns and consequences. Developing new technologies improves detection of these DNA variations, crucial for disease research.

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Area of Science:

  • Genomics
  • Human Biology
  • Molecular Biology

Background:

  • Somatic mutations, DNA variations acquired after fertilization, occur due to replication errors or mutagens.
  • Understanding somatic mutation frequency, type, and patterns in healthy tissues is limited.
  • Detecting low-proportion somatic variants is challenging compared to inherited variants.

Purpose of the Study:

  • To create a reference catalogue of somatic mutations and clonal patterns in 19 human tissue sites from 150 healthy donors.
  • To develop advanced technologies and computational tools for somatic mutation detection.
  • To assess phenotypic consequences of somatic mutations, including clonal expansions.

Main Methods:

  • Established the Somatic Mosaicism across Human Tissues Network.
  • Collected samples from 150 non-diseased individuals across 19 tissue types.
  • Developed novel detection and analysis methods for somatic variants and clonal architecture.

Main Results:

  • Generated a comprehensive catalogue of somatic mutations across diverse human tissues.
  • Identified distinct patterns of somatic mutations and clonal expansions.
  • Established a baseline for somatic mutation analysis in healthy individuals.

Conclusions:

  • Provides a foundational understanding of the somatic mutational landscape in humans.
  • Enables comparison with somatic mutation patterns in various diseases.
  • Facilitates deeper insights into somatic mutations and clonal expansions throughout the lifespan, in aging, and disease.