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Human organoids – three-dimensional structures of cells that recapitulate important aspects of organ development in vitro – hold tremendous potential for biomedical applications. To help deliver on the promises of combining human organoids with single-cell technology, we have launched an Organoid Cell Atlas pilot project, as a 'Biological Network' within the Human Cell Atlas (HCA), focusing on single-cell profiling of organoids and in vitro cell models (https://www.humancellatlas.org/coordinators/). The Organoid Cell Atlas will foster the production, quality control, dissemination, and utilization of single-cell and spatial genomics data for human organoids, and it will connect such datasets with the comprehensive profiles of primary tissue that are being generated within the HCA. A first step toward establishing the Organoid Cell Atlas has recently been funded by the European Union Horizon 2020 call for "Pilot actions to build the foundations of a human cell atlas" through the "HCA|Organoid" project (http://hca-organoid.eu/). This preprint outlines the rationale for combining human organoids with single-cell technology and the concrete plans for established the Organoid Cell Atlas as a Rosetta Stone for biomedical discovery and regenerative therapy.

Long-range interactions between regulatory elements and gene promoters play key roles in transcriptional regulation. The vast majority of interactions are uncharted, constituting a major missing link in understanding genome control. Here, we use promoter capture Hi-C to identify interacting regions of 31,253 promoters in 17 human primary hematopoietic cell types. We show that promoter interactions are highly cell type specific and enriched for links between active promoters and epigenetically marked enhancers. Promoter interactomes reflect lineage relationships of the hematopoietic tree, consistent with dynamic remodeling of nuclear architecture during differentiation. Interacting regions are enriched in genetic variants linked with altered expression of genes they contact, highlighting their functional role. We exploit this rich resource to connect non-coding disease variants to putative target promoters, prioritizing thousands of disease-candidate genes and implicating disease pathways. Our results demonstrate the power of primary cell promoter interactomes to reveal insights into genomic regulatory mechanisms underlying common diseases. ; This work was supported by the following grants: UK Medical Research Council (MR/L007150/1, MC_UP_1302/1, MC_UP_1302/3, MC_UP_1302/5), UK Biotechnology and Biological Sciences Research Council (BB/J004480/1), ERC (DEVOCHROMO advanced grant), JDRF (9-2011-253, 5-SRA-2015-130), Wellcome Trust (089989, 091157, 095908, 100140, 107212, 107881), European Union 7th Framework Programme (FP7/2007-2013, grant agreements 241447 [NAIMIT] and 282510 [BLUEPRINT]), NHS Blood and Transplant, NIHR (PG-0310-1002), and BHF (RG/09/12/28096). K.D. is funded by NHS Health Education England. M.F. is supported by the BHF Cambridge Centre of Excellence (RE/13/6/30180). S.P.W., M.K., D.R.Z., and O.S. are funded by the European Molecular Biology Laboratory. ; This is the final version of the article. It first appeared from Elsevier (Cell Press) via https://doi.org/10.1016/j.cell.2016.09.037