Novel Technologies to Query Single Cells in Hematopoiesis

The hematopoietic system comprises a complex hierarchy of cell lineages starting from hematopoietic stem cells to common myeloid and lymphoid progenitors and to all major blood cell types. Recent breakthroughs in single-cell omics technologies further revealed a high degree of cellular heterogeneity in each population, identified new subpopulations, and allowed to define their biological functions in normal hematopoiesis or hematologic malignancies. Single-cell genomic, transcriptomic, mass cytometric, and protein secretomic analyses allow us to query single cells in a high-throughput manner and at all the levels of the central dogma, providing unprecedented resolution toward improved understanding of hematopoiesis in human health and disease.

Dr. Satija will present recent developments in single-cell sequencing, and their application to hematopoiesis. Recent developments in single cell transcriptomics, for example, allow for the sequencing of tens of thousands of cells from complex tissues, and enable the unbiased identification of cellular subpopulations as well as the reconstruction of developmental hierarchies. Dr. Satija will discuss the application of Drop-seq to reconstruct lineages in human hematopoiesis, and highlight the potential for single cell sequencing to uncover key regulators of cell fate decisions in both health and disease.

Dr. Fan will discuss novel single-cell technologies for functional proteomic profiling including single-cell, 42-plex cytokine secretion measurement for interrogating hematopoietic cells from patients with myeloproliferative disease identified a polyfunctional pathogenic subpopulation. Single-cell data resolved that both “normal” and “malignant” hematopoietic cells show abnormal cytokine functions, contributing to pathogenesis and therapeutic response. The results underscore the importance of measuring functional proteomic heterogeneity even in phenotypically identical cell populations and provide a new tool potentially for more accurate diagnosis or monitoring of hematologic malignancies.