Over the past decade, single-cell genomics technologies have allowed scalable profiling of cell-type-specific features, which has substantially increased our ability to study cellular diversity and transcriptional programs in heterogeneous tissues. Yet our understanding of mechanisms of gene regulation or the rules that govern interactions between cell types is still limited. The advent of new computational pipelines and technologies, such as single-cell epigenomics and spatially resolved transcriptomics, has created opportunities to explore two new axes of biological variation: cell-intrinsic regulation of cell states and expression programs and interactions between cells. Here, we summarize the most promising and robust technologies in these areas, discuss their strengths and limitations and discuss key computational approaches for analysis of these complex datasets. We highlight how data sharing and integration, documentation, visualization and benchmarking of results contribute to transparency, reproducibility, collaboration and democratization in neuroscience, and discuss needs and opportunities for future technology development and analysis.
GrantsSwedish Research Council HHMI Emerging Pathogens Initiative Sontag Foundation James S. McDonnell Foundation 21st Century Science Initiative in Understanding Human Cognition Carol and Gene Ludwig Family Foundation Simons Foundation NHGRI NINDS NIMH JPB Foundation Picower Institute Innovation Fund Helmholtz Center Munich, DFG priority program ERA-NET Neuron (MOSAIC) Shurl and Kay Curci Foundation Esther A & Joseph Klingenstein Fund Knut and Alice Wallenberg Foundation Swedish Brain Foundation Swedish Society for Medical Research (SSMF) Goran Gustafsson Foundation for Research in Natural Sciences and Medicine National Institutes of Health (NIH) NIH European Research Council Consolidator grant Israel Science Foundation Belfer Neurodegeneration Consortium Cure Alzheimer's Fund European Research Council European Union (ERC) Wellcome Sanger core Wellcome LEAP funding National Institute of General Medical Sciences of the NIH NINDS Intramural funds Lieber Institute for Brain Development European Research Council (ERC) National Multiple Sclerosis Society German Research Foundation through collaborative research projects Heisenberg Fellowship