Epigenetic barcoding incorporating Tapestri unlocks high-throughput single-cell lineage tracing of clonality with or without mutation drivers, a previously invisible precursor to cancer development
EPI-clone, developed by researchers at Centre for Genomic Regulation and Institute for Research in Biomedicine, tracks clonal dynamics in hematopoiesis with naturally occurring DNA methylation patterns, laying the groundwork for discovering new cancer progression mechanisms and therapeutic targets
SOUTH SAN FRANCISCO, Calif.–(BUSINESS WIRE)–Mission Bio, a leader in single-cell multiomics solutions for precision medicine, today announced a new publication in Nature leveraging its Tapestri Platform to develop a single-cell barcoding method for high-throughput cell lineage tracing. Study leader Lars Velten and his team at Spain’s Centre for Genomic Regulation (CRG), working with a group led by Alejo Rodriguez-Fraticelli at the Institute for Research in Biomedicine (IRB), used Tapestri as a basis to develop EPI-clone, which combines single-cell multi-omics with the readout of naturally occurring DNA methylation patterns as molecular barcodes for tracing clonality – the rapid proliferation of specific cells that precedes development of cancer. The method could be used to identify drug targets on pre-cancer clones that prevent disease progression, like methylation patterns as for epigenetic drugs like DNA methylation transferase inhibitors.
Lineage tracing holds the potential to explain how premalignant conditions like clonal hematopoiesis of indeterminate potential (CHIP) and myelodysplastic syndrome (MDS) can progress into hematologic cancers, and how cancerous subclones persist in relapse. Traditional methods for lineage tracing can be complex, low-throughput, or even harmful to normal cellular function. In the paper, titled «Clonal tracing with somatic epimutations reveals dynamics of blood aging,» EPI-clone utilizes natural epigenetic patterns that are highly stable over long time scales.
Using Mission Bio’s Tapestri Platform for high-throughput multi-omics measurement, researchers successfully captured hundreds of clonal differentiation trajectories across 230,358 single cells in both mouse and human hematopoiesis, with dual readout of epimutational barcodes and cell state information.
“EPI-clone provides insights into clonal selection during aging, potentially guiding the development of personalized, preventative treatments for diseases like cancers,” said Velten. “The scale of our findings could only have been enabled by Tapestri, which allowed us simultaneous observation of single-cell genotype, phenotype, and clone.”
“The impressive results of this study are a first step toward truly identifying, and therefore understanding, how certain clones contribute to cancer progression before they expand,” said Adam Sciambi, Chief Technology Officer at Mission Bio. “We look forward to continued collaboration with the CRG team and others as we support the use of the Tapestri Platform’s unique capabilities to make novel discoveries that change the course of disease understanding and treatment.”
In aging mice, the researchers found that low output of old hematopoietic stem cells (HSCs) is restricted to a small number of expanded clones, while many functionally young clones persist in old age. In human aging, the team showed that clones associated with known clonal hematopoiesis (CH) mutations are part of a broader spectrum of age-related clonal expansions, with and without known driver mutations, displaying similar lineage biases. The results also showed that clonal complexity declines with age, leading to oligoclonal blood production.
To learn more about Tapestri and its ability to provide single-cell DNA + protein analysis at unmatched resolution, please visit missionbio.com/products/platform/.
About Mission Bio
Mission Bio is a leading life science company, specializing in the advancement of single-cell DNA and multiomics analysis. The company’s Tapestri Platform is unique in its capabilities, offering an unparalleled level of granularity and precision that is critical for complex research areas such as cancer studies, pharmaceutical development, and advanced cell and gene therapies. Unlike traditional methods such as bulk sequencing, Tapestri provides a level of precision that opens the door for more tailored and effective treatment strategies. Researchers globally depend on Tapestri to identify rare cell populations, understand mechanisms of therapeutic resistance and response, and establish key quality metrics for next-generation medical treatments. Founded in 2014, Mission Bio has secured investment from firms including Mayfield Fund, Novo Growth, Cota Capital, and Agilent Technologies. With the Tapestri Platform, Mission Bio is setting the standard in the field, contributing significantly to the progress of personalized medicine and targeted therapies. To learn more about Mission Bio and the Tapestri Platform, please visit missionbio.com.
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