Emerging technologies of single-cell multi-omics

The heterogeneity of the hematopoietic system was largely veiled by traditional bulk sequencing methods, which measure the averaged signals from mixed cellular populations. In contrast, single-cell sequencing has enabled the direct measurement of individual signals from each cell, significantly enhancing our ability to unveil such heterogeneity. Building on these advances, numerous single-cell multi-omics techniques have been developed into high-throughput, routinely accessible platforms, delineating the precise relationships among different layers of the central dogma in molecular biology. These technologies have uncovered the intricate landscape of genetic clonality and transcriptional heterogeneity in both normal and malignant hematopoietic systems, highlighting their roles in differentiation, disease progression, and therapy resistance. This review aims to provide a brief overview of the principles of single-cell technologies, their historical development, and a subset of ever-expanding multi-omics tools, emphasizing the specific research questions that inspired their creation. Amidst the evolving landscape of single-cell multi-omics technologies, our main objective is to guide investigators in selecting the most suitable platforms for their research needs.