Single-cell RNA sequencing (scRNA-seq) technologies are poised to reshape the current cell-type classification system. However, a transcriptome-based single-cell atlas has not been achieved for complex mammalian systems. Here, we developed Microwell-seq, a high-throughput and low-cost scRNA-seq platform using simple, inexpensive devices. Using Microwell-seq, we analyzed more than 400,000 single cells covering all of the major mouse organs and constructed a basic scheme for a mouse cell atlas (MCA). We reveal a single-cell hierarchy for many tissues that have not been well characterized previously. We built a web-based "single-cell MCA analysis" pipeline that accurately defines cell types based on single-cell digital expression. Our study demonstrates the wide applicability of the Microwell-seq technology and MCA resource.

Hematopoiesis is probably the best-understood stem cell differentiation system; hematopoietic stem cell (HSC) transplantation represents the most widely used regenerative therapy. The classical view of lineage hierarchy in hematopoiesis is built on cell type definition system by a group of cell surface markers. However, the traditional model is facing increasing challenges, as many classical cell types are proved to be heterogeneous. Recently, the developments of new technologies allow genome, transcriptome, proteome, and epigenome analysis at the single-cell level. For the first time, we can study hematopoietic system at single-cell resolution on a multi-omic scale. Here, we review recent technical advances in single-cell analysis technology, as well as their current applications. We will also discuss the impact of single-cell technologies on both basic research and clinical application in hematology.

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