Volume 2 Issue 9, September 2023

Spatially resolved multiomics is an emerging approach for profiling gene expression at the cellular level while maintaining the spatial organization of tissues. Its application in healthy human hearts provides insight into ion channels and regulatory signaling in the cardiac conduction system, cardiac cellular niches and drug–cell interactions.

A method to identify and analyze clonal hematopoiesis in clinical blood samples at single-cell resolution reveals cell-intrinsic and paracrine effects of DNMT3A mutations in circulating monocytes, T cells and natural killer cells in the setting of heart failure.

Lipid remodeling, from fatty acid transport and de novo lipid synthesis, is necessary for megakaryocyte differentiation and platelet production. Dietary saturated fatty acids, impaired fatty acid transport and/or dysfunction in lipid biogenesis can contribute to low platelet counts.

Rauch et al. show that loss-of-function mutations in the epigenetic regulator Dnmt3a lead to accelerated atherosclerosis, as previously shown for Tet2, and that loss of either gene leads to similar changes in atheroma composition, with the emergence of a distinct population of chemokine-enriched, resident-like macrophages infiltrating the adventitia, as revealed by single-cell transcriptomics and spatial proteomic analyses.

Abplanalp et al. define the transcriptome of cells carrying mutations in a specific gene at a single-cell level (MutDetect-Seq) and apply it to reveal the cell-intrinsic effects of mutations in DNMT3A associated with clonal hematopoiesis in patients with heart failure.

de Jonckheere, Kollotzek, et al. report a quantitative proteomic and lipidomic map of different stages of megakaryopoiesis and find an anionic lipid membrane remodeling and concomitant relocalization of the CKIP-1/CK2α complex to the plasma membrane of maturing megakaryocytes, which appear to be essential for sufficient platelet biogenesis.