In a randomized, placebo-controlled, phase 2 trial, oral vitamin C did not alter clonal growth rate in patients with clonal cytopenia of undetermined significance or lower risk myeloid malignancies b...

This study shows that clonal hematopoiesis expands after chimeric antigen receptor (CAR) T cell therapy and contributes to secondary myeloid cancers. In addition, the CAR vector frequently integrates ...

This study shows that clonal hematopoiesis expands after chimeric antigen receptor (CAR) T cell therapy and contributes to secondary myeloid cancers. In addition, the CAR vector frequently integrates ...

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Solomonidis et al. reveal that hematopoietic KDM6A-driven clonal hematopoiesis worsens post-MI cardiac recovery by promoting inflammatory myeloid reprogramming. IL-1β blockade reverses these adverse e...

Read the full paper: A stress-adapted fiber state promotes clonal expansion of deleted mitochondrial DNA

Plants maintain remarkable regenerative potential, yet this capacity declines with developmental age, limiting clonal propagation and biotechnological applications. Here, we show that the miR172-AP2 ...

Destructive sampling in single-cell sequencing obscures ancestor-descendant relationships, limiting the continuous reconstruction of cell-fate dynamics. Here we present Lineage-aware optimal transport for unbalanced single-cell dynamics (LOTUS), a framework that integrates time-resolved transcriptomic snapshots with clonal lineage information from engineered barcodes or endogenous T cell receptor clonotypes. LOTUS couples clone-level optimal transport with neural unbalanced transport to model continuous cellular state change, population growth and clonal propagation under lineage-consistent constraints. In branching simulations, LOTUS reduced lineage-inconsistent transport relative to benchmark methods, lowering off-target routing from 4.94-14.84% to 1.10%. On LARRY lineage-barcode scRNA-seq of hematopoiesis, LOTUS reconstructed branching trajectories, improved early neutrophil-monocyte fate-boundary prediction, and inferred multi-fate progenitors and fate-biased meta-clones, linking their distinct fate potentials to inferred epigenetic priming. On CellTagging scRNA-seq of fibroblast reprogramming, it distinguished reprogrammed from failed trajectories and prioritized fate-associated perturbation genes. In longitudinal scRNA-seq and TCR-seq of malaria-responsive memory (CD45RA-) CD4+ T cells, it preserved endogenous clonotype structure and reconstructed TR1 dynamics and regulatory networks. LOTUS thus converts lineage-resolved single-cell snapshots into interpretable, continuous models of fate dynamics and their regulatory programs.

In this Review, Izzo et al. discuss how single-cell multimodal sequencing enables genotype–phenotype mapping and, when combined with phylogenetic reconstruction, provide insights into clonal evolution, cell state plasticity, and cancer progression, revealing mutant-specific vulnerabilities and offering a framework to study somatic evolution across pre-malignant and malignant human tissues.