• HOME
  • NEWS
  • EXPLORE
    • CAREER
      • Companies
      • Jobs
    • EVENTS
    • iGEM
      • News
      • Team
    • PHOTOS
    • VIDEO
    • WIKI
  • BLOG
  • COMMUNITY
    • FACEBOOK
    • INSTAGRAM
    • TWITTER
Saturday, August 2, 2025
BIOENGINEER.ORG
No Result
View All Result
  • Login
  • HOME
  • NEWS
  • EXPLORE
    • CAREER
      • Companies
      • Jobs
        • Lecturer
        • PhD Studentship
        • Postdoc
        • Research Assistant
    • EVENTS
    • iGEM
      • News
      • Team
    • PHOTOS
    • VIDEO
    • WIKI
  • BLOG
  • COMMUNITY
    • FACEBOOK
    • INSTAGRAM
    • TWITTER
  • HOME
  • NEWS
  • EXPLORE
    • CAREER
      • Companies
      • Jobs
        • Lecturer
        • PhD Studentship
        • Postdoc
        • Research Assistant
    • EVENTS
    • iGEM
      • News
      • Team
    • PHOTOS
    • VIDEO
    • WIKI
  • BLOG
  • COMMUNITY
    • FACEBOOK
    • INSTAGRAM
    • TWITTER
No Result
View All Result
Bioengineer.org
No Result
View All Result
Home NEWS Science News Technology

Tracing Blood Aging Through Somatic Epimutations

Bioengineer by Bioengineer
May 21, 2025
in Technology
Reading Time: 4 mins read
0
Share on FacebookShare on TwitterShare on LinkedinShare on RedditShare on Telegram

blank

In the quest to decode the intricate landscape of human aging at the cellular level, groundbreaking research now reveals a novel approach to trace the lineage and expansion of blood cell clones by harnessing epigenetic signatures. The method, termed EPI-Clone, offers an unprecedented view into the dynamics of hematopoietic stem and progenitor cells (HSPCs) within human bone marrow, laying bare the clones that fuel both normal blood development and age-associated clonal hematopoiesis (CH). This approach not only amplifies our understanding of blood aging but also unearths the subtle interplay between genetic mutations and epigenetic modifications that drive clonal expansions over time.

At the core of this innovation is the design of a targeted methylation panel focusing on 448 CpG sites known to exhibit variable methylation either between or within blood progenitor populations. This high-resolution panel allows for a precise capture of epimutations—heritable, somatic changes in DNA methylation patterns—that act as natural barcodes for tracing cellular lineage. Complementing this, the inclusion of 147 genomic regions frequently mutated in clonal hematopoiesis and 20 regions targeting the Y chromosome offers a robust ground truth against which the epigenetic clones identified with EPI-Clone can be validated.

The researchers applied this panel to CD34⁺-enriched total bone marrow samples collected from seven human donors of diverse ages, spanning a spectrum from young adults to the elderly. Alongside this, an expanded set of CD34⁺ cells was assembled from multiple donors to strengthen the dataset. The meticulous profiling of 135,432 single cells using scTAM-seq—a single-cell targeted methylation sequencing technique—enabled comprehensive scrutiny of both genetic mutations and epigenetic states. The samples were concurrently characterized by staining with a battery of 45 antibodies targeting surface proteins, thereby enriching the phenotypic context of the epigenetic data.

Leveraging a statistical framework known as CHOIR (Clonal Hematopoiesis Outlier Identification in R), the study sifted through the heterogeneous single-cell data to detect expanded clones, carefully combining epigenetic signatures and surface marker expression to delineate cell types and differentiation states. This dual-layered analysis refined the identification of clones, ensuring that both dynamic CpGs—those changing during differentiation—and robust phenotypic markers scouted by the antibody panel contributed to clone definition.

Validation of this intricate approach came from the detection of canonical CH mutations and loss of Y chromosome (LoY) events, which served as internal clonal markers. Consistently, clones bearing these somatic mutations grouped tightly together in reduced-dimensionality embeddings based solely on static CpG methylation patterns. This concordance affirms the fidelity of epigenetic marks as reliable surrogates for underlying genetic clonal identity. Notably, clones identified by EPI-Clone aligned well with known CH clones in nearly all donors, barring one with considerably fewer sampled cells, underscoring the importance of adequate cellular representation for accurate clonal mapping.

Quantitative analyses revealed that clonal populations driven by CH mutations consisted predominantly of mutant cells—averaging about 78.8%—while wild-type dominated clones exhibited an average purity exceeding 95%. These values are conservative estimates given potential allelic dropout in mutation detection at the single-cell level. Importantly, the method proved more adept at discerning clones in older individuals, who typically harbor less diverse hematopoietic pools due to accumulated clonal expansions, suggesting that epigenetic tracing performs optimally amidst reduced clonal complexity seen in aging hematopoiesis.

Beyond uncovering clones with known CH drivers, EPI-Clone unveiled a broader spectrum of 67 additional clonal expansions across the cohort, revealing a hidden landscape of hematopoietic diversity untouched by previously characterized mutations. This observation hints at the presence of unknown or subclonal drivers contributing to hematopoietic architecture or reflects the stochastic nature of epigenetic drift within the blood system.

The analysis extended to different immune cell types, confirming that natural killer cells and immature B cells also segregate predictably by clonal identity in accordance with their methylation profiles. T cells and mature B cells formed distinct, lymphoid-dominant clusters that diverged from myeloid-origin clones, illustrating separate ontogenetic trajectories within hematopoiesis. Intriguingly, in one donor with a large CH clone, mutant T cells clustered tightly with other CH-derived cells, suggesting that some mutated clones contribute broadly across lineages, reinforcing the notion of clonal stability from hematopoietic stem cells through multiple lineages including myeloid, T cells, NK cells, and immature B cells.

By establishing a conservative lower bound for EPI-Clone’s sensitivity, the group identified the smallest detectable CH clone, harboring a DNMT3A(C666Y) mutation, comprising 145 cells and representing about 1% of the myeloid compartment in one donor. Furthermore, notable diversification within large CH clones, such as the DNMT3A(R659H) mutation carrier, manifested as bifurcated epigenetic subclones with distinct but related static CpG profiles. This insight suggests that epimutations accrue progressively over time, refining phylogenetic resolution and providing a longitudinal record of clonal evolution spanning decades.

Together, these findings underscore EPI-Clone’s capacity to chart the nuanced topography of hematopoietic clonal expansions in human bone marrow and blood. By integrating high-dimensional epigenetic and phenotypic data with somatic mutation analyses, the approach extends our ability to dissect blood aging at unparalleled detail. It offers promise for elucidating the role of clonal hematopoiesis in age-related diseases and potentially guiding precision interventions targeting aberrant clonal dynamics.

This pioneering work melds cutting-edge single-cell epigenomics with rigorous statistical modeling, capturing a snapshot of blood’s evolutionary history etched into the methylome. As the field advances, EPI-Clone could catalyze transformative insights into hematological health and disease, driving a new era of clonal blood biology with far-reaching implications for aging research, cancer biology, and regenerative medicine.

Subject of Research: Clonal dynamics of human hematopoietic stem and progenitor cells during aging, traced via somatic epimutations and mutational profiling.

Article Title: Clonal tracing with somatic epimutations reveals dynamics of blood ageing.

Article References:
Scherer, M., Singh, I., Braun, M.M. et al. Clonal tracing with somatic epimutations reveals dynamics of blood ageing. Nature (2025). https://doi.org/10.1038/s41586-025-09041-8

Image Credits: AI Generated

Tags: age-associated clonal expansionsblood aging researchclonal hematopoiesis mechanismsDNA methylation patterns in bloodEPI-Clone methodologyepigenetic signatures in blood cellsgenetic and epigenetic interactionshematopoietic stem cell dynamicshigh-resolution epigenetic analysislineage tracing of blood progenitor cellssomatic epimutations in agingtargeted methylation panel design

Share12Tweet8Share2ShareShareShare2

Related Posts

Revolutionary AI Tool Requires Minimal Data to Analyze Medical Images

Revolutionary AI Tool Requires Minimal Data to Analyze Medical Images

August 1, 2025
Newborn Brain Development: Plateau vs. Plain Insights

Newborn Brain Development: Plateau vs. Plain Insights

August 1, 2025

Revolutionizing Task Planning: The Impact of Large Language Models on Future Strategies

August 1, 2025

Revolutionary AI Technology Paves the Way for Innovative Materials to Replace Lithium-Ion Batteries

August 1, 2025

POPULAR NEWS

  • Blind to the Burn

    Overlooked Dangers: Debunking Common Myths About Skin Cancer Risk in the U.S.

    60 shares
    Share 24 Tweet 15
  • Dr. Miriam Merad Honored with French Knighthood for Groundbreaking Contributions to Science and Medicine

    46 shares
    Share 18 Tweet 12
  • Neuropsychiatric Risks Linked to COVID-19 Revealed

    38 shares
    Share 15 Tweet 10
  • Study Reveals Beta-HPV Directly Causes Skin Cancer in Immunocompromised Individuals

    38 shares
    Share 15 Tweet 10

About

We bring you the latest biotechnology news from best research centers and universities around the world. Check our website.

Follow us

Recent News

Unraveling EMT’s Role in Colorectal Cancer Spread

Gut γδ T17 Cells Drive Brain Inflammation via STING

Agent-Based Framework for Assessing Environmental Exposures

  • Contact Us

Bioengineer.org © Copyright 2023 All Rights Reserved.

Welcome Back!

Login to your account below

Forgotten Password?

Retrieve your password

Please enter your username or email address to reset your password.

Log In
No Result
View All Result
  • Homepages
    • Home Page 1
    • Home Page 2
  • News
  • National
  • Business
  • Health
  • Lifestyle
  • Science

Bioengineer.org © Copyright 2023 All Rights Reserved.