Large-scale single-cell RNA sequencing atlases of human immune cells across lifespan: Possibilities and challenges

Abstract

Single-cell RNA sequencing technologies have successfully been leveraged for immunological insights into human prenatal, pediatric, and adult tissues. These single-cell studies have led to breakthroughs in our understanding of stem, myeloid, and lymphoid cell function. Computational analysis of fetal hematopoietic tissues has uncovered trajectories for T- and B-cell differentiation across multiple organ sites, and how these trajectories might be dysregulated in fetal and pediatric health and disease. As we enter the age of large-scale, multiomic, and integrative single-cell meta-analysis, we assess the advances and challenges of large-scale data generation, analysis, and reanalysis, and data dissemination for a broad range of scientific and clinical communities. We discuss Findable, Accessible, Interoperable, and Reusable data sharing and unified cell ontology languages as strategic areas for progress of the field in the near future. We also reflect on the trend toward deployment of multiomic and spatial genomic platforms within single-cell RNA sequencing projects, and the crucial role these data types will assume in the immediate future toward creation of comprehensive and rich single-cell atlases. We demonstrate using our recent studies of human prenatal and adult hematopoietic tissues the importance of interdisciplinary and collaborative working in science to reveal biological insights in parallel with technological and computational innovations.

Keywords: Bioinformatics; Hematopoiesis; Multiomics; Single-cell RNA sequencing; Single-cell genomics.