Wellcome/MRC Cambridge Stem Cell Institute

Dynamics of human cardiogenesis and its disruption in trisomy 21

Abstract Developmental dynamics involve the specification of diverse cell types and their spatial organization into multicellular niches 1 . Here we combine single-cell and spatial multiomics to define 21 distinct tissue niches in the developing heart, which we use to develop a c...

Spatially resolved multiomics of human meningeal development reveal lineage and disease dynamics

Abstract The meninges are increasingly recognized as key stromal and immune niches supporting cranial development. Here we constructed a paired single-nuclei RNA and Assay for Transposase-Accessible Chromatin atlas of human meningeal development from 6 to 21 postconception weeks...

A step-wise, deterministic and fatal mouse model of myeloid neoplasm with spontaneous acquisition of patient-relevant RTK–RAS mutations

Abstract Leukaemia arises through the stepwise transformation of healthy haematopoietic cells, yet the asymptomatic premalignant phase and its progression to overt disease remain poorly understood. To model this process, we engineered a patient-derived CEBPA mutation into Hoxb8-F...

Weighted sliced inverse regression for scalable supervised dimensionality reduction of spatial transcriptomics data

Abstract With the dramatic take-up of spatially resolved transcriptomics biotechnologies, performing spatially-aware analysis of the resulting data is crucial to maximise advances in biological understanding. Dimensionality reduction is a first step in almost any analysis of spat...

Activation of transposable elements is linked to a region- and cell type–specific interferon response in Parkinson’s disease

Abstract Parkinson’s disease (PD) is a neurodegenerative disorder involving a neuroinflammatory response, the cause of which remains unclear. Transposable elements (TE) have been linked to inflammation, but their potential role in PD remains unexplored. Using bulk- and single-nuc...

Machine learning provides individualized prediction of outcomes after first complete remission without allo‐HSCT consolidation in adult acute myeloid leukemia—A HARMONY study

Abstract Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is a curative treatment option for a significant proportion of patients with acute myeloid leukemia (AML), and it is generally recommended when the relapse risk without allo‐HSCT outweighs the estimated non‐r...

Charting Endocrine Progenitors Across Species and Organs

ABSTRACT Hormone‐producing cells in the pancreas and intestine regulate whole‐body metabolism and are dysregulated in obesity and diabetes. A deeper understanding of endocrine lineage formation (endocrinogenesis) in these organs is essential to elucidate the healthy state and dis...

The RNA helicase domain of NAT10 promotes the biogenesis of hypomodified ribosomes to enhance cancer cell proliferation

Abstract N-acetyltransferase 10 (NAT10) is a multifunctional enzyme that harbors RNA acetyltransferase and RNA helicase domains and has emerged as a therapeutic vulnerability in solid and hematological malignancies. By coupling Proteolysis Targeting Chimera-mediated degradation o...

Reversible epiblast regionalization determines differentiation potential of human pluripotent stem cells

Abstract Although human pluripotent stem cells (hPSCs) can generate all tissues of the body, hPSCs in vitro frequently exhibit differentiation biases or failure that pose substantial challenges for disease modeling and regenerative medicine. The origins of these biases remain inc...