Deciphering cell states and genealogies of human haematopoiesis.

The human blood system is maintained through the differentiation and massive amplification of a limited number of long-lived haematopoietic stem cells (HSCs)1. Perturbations to this process underlie diverse diseases, but the clonal contributions to human haematopoiesis and how this changes with age remain incompletely understood. Although recent insights have emerged from barcoding studies in model systems2-5, simultaneous detection of cell states and phylogenies from natural barcodes in humans remains challenging. Here we introduce an improved, single-cell lineage-tracing system based on deep detection of naturally occurring mitochondrial DNA mutations with simultaneous readout of transcriptional states and chromatin accessibility. We use this system to define the clonal architecture of HSCs and map the physiological state and output of clones. We uncover functional heterogeneity in HSC clones, which is stable over months and manifests as both differences in total HSC output and biases towards the production of different mature cell types. We also find that the diversity of HSC clones decreases markedly with age, leading to an oligoclonal structure with multiple distinct clonal expansions. Our study thus provides a clonally resolved and cell-state-aware atlas of human haematopoiesis at single-cell resolution, showing an unappreciated functional diversity of human HSC clones and, more broadly, paving the way for refined studies of clonal dynamics across a range of tissues in human health and disease.

Trends in Location of Death for Individuals With Ovarian Cancer in the United States.

Using the publicly available Centers for Disease Control and Prevention's WONDER (Wide-ranging Online Data for Epidemiologic Research) database from 2003 to 2019, we evaluated associations between decedent characteristics and location of death for patients with ovarian malignancy. We found that Black, Native American, Asian American, and Hispanic patients were more likely to die in hospitals than White patients, despite an overall reduction in hospital deaths and an overall increase in hospice facility deaths. Additionally, patients with lesser educational attainment were more likely to die in nursing facilities and less likely to die in hospice facilities. Although there may be some contribution from cultural preferences, these findings may represent disparities in access to palliative care affecting people with cancer from racial and ethnic minoritized groups.

Harnessing big data for health equity through a comprehensive public database and data collection framework.

The United States Department of Health and Human Services (HHS) pledged $90 million to help reduce health disparities with data-driven solutions. The funds are being distributed to 1400 community health centers, serving over 30 million Americans. Given these developments, our piece examines the reasons behind the delayed adoption of big data for healthcare equity, recent efforts embracing big data tools, and methods to maximize potential without overburdening physicians. We additionally propose a public database for anonymized patient data, introducing diverse metrics and equitable data collection strategies, providing valuable insights for policymakers and health systems to better serve communities.