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.

A deep single-cell and spatial multi-omic atlas of human glioblastoma is generated, pairing transcriptomic, epigenomic and genomic profiling, and tracing glioblastoma tumour heterogeneity to a st...

Gene network analysis shows how mutations in diverse genes associated with autism spectrum disorder can converge to exert shared effects, with X-linked transcription factor ZFX emerging as a key prote...

CasRx17, specifically NLS-RfxCas13d-NLS (Addgene, 109049), was used in combination with target-specific gRNAs for KD of targeted transcripts. A deep-learning-based tool66 was used to design gRNA spacer sequences targeting the genes of interest. These spacer sequences were filtered to exclude homopolymers (more than four As, more than three Cs, Gs or Ts). Spacer sequences with potential off-target interactions were identified using BLAST67 and excluded. For each target gene, three separate spacer sequences were selected and combined into a tandem pre-gRNA array, with each spacer sequence preceded by the CasRx direct repeat (DR36) sequence66: CAAGTAAACCCCTACCAACTGGTCGGGGTTTGAAAC. Tandem pre-gRNA arrays were processed by CasRx into individual gRNAs for KD17. See Supplementary Table 1 for full sequences. Molecular cloning To create constructs for the initial NPC KD experiments, we used the lentiviral pSicoR plasmid68 (Addgene, 11579) as the backbone. The mouse U6 promoter was replaced with the human U6 promoter, which was used to drive expression of the CasRx gRNA arrays. These constructs were used in combination with a CasRx knock-in cell line (described below). To obtain enough NPCs for CasRx KD validation by auto-western blot (described below), an all-in-one construct was created that contained CasRx and EGFP expressed from the CAG promoter element and...

The hippocampal-entorhinal system supports cognitive functions, has lifelong neurogenic capabilities in many species, and is selectively vulnerable to…

A deep single-cell and spatial multi-omic atlas of human glioblastoma is generated, pairing transcriptomic, epigenomic and genomic profiling, and tracing glioblastoma tumour heterogeneity to a st...

Compared with mouse cells, tree shrew fibroblasts more faithfully recapitulate the hallmarks of human cellular senescence. In vivo, aged tree shrews exhibit transcriptomic signatures of aging across ...

Quantro Therapeutics GmbH, a Vienna, Austria-based provider of a transcriptomic drug discovery and R&D platform targeting transcription factors, received