Single-cell proteo-genomic reference maps of the hematopoietic system enable the purification and massive profiling of precisely defined cell states

Abstract

Single-cell genomics has transformed our understanding of complex cellular systems. However, excessive costs and a lack of strategies for the purification of newly identified cell types impede their functional characterization and large-scale profiling. Here, we have generated high content single-cell proteo-genomic reference maps of human blood and bone marrow that quantitatively link the expression of up to 197 surface markers to cellular identities and biological processes across all hematopoietic cell types in healthy aging and leukemia. These reference maps enable the automatic design of cost-effective high-throughput cytometry schemes that outperform state-of-the-art approaches, accurately reflect complex topologies of cellular systems, and permit the purification of precisely defined cell states. The systematic integration of cytometry and proteo-genomic data enables the interpretation of functional capacities of such precisely mapped cell states at the single-cell level. Our study serves as an accessible resource and paves the way for a data-driven era in cytometry.

Single-cell RNA sequencing identifies phenotypically, functionally, and anatomically distinct stromal niche populations in human bone marrow

“…Due to the low frequencies of the stromal stem/progenitor cells, it has been difficult to investigate the potential heterogeneity of the human BM stromal cell compartment even when employing single cell approaches (Triana et al, 2021). In this study, we therefore used not only BM stroma-enriched CD45 low/- CD235a - cells but added also sorted CD271 + cells, which are highly and exclusively enriched for stromal stem/progenitor cells (Tormin et al, 2011).…”

Uncovering perturbations in human hematopoiesis associated with healthy aging and myeloid malignancies at single cell resolution

“…In this study we report the generation of high-resolution scRNA maps of human HSPCs and the changes associated with aging. Although previous studies focused on other species (22,43) and other layers of information such as mutations (44), proteomics (45), and proteo-genomics (46), our study represents one of the first analyses that describes early human hematopoiesis based on its dynamic gene expression and transcriptional regulation by identifying age related changes that may be responsible for some of the phenotypic modifications observed during healthy aging. Applying this knowledge to HSPCs obtained from patients with AML and MDS, we establish as a proof of concept of how this analysis has the potential to help identifying transcriptional alterations that play potential roles during disease development, which may eventually lead to the identification of potential therapeutic targets.…”

Dynamic Changes of the Bone Marrow Niche: Mesenchymal Stromal Cells and Their Progeny During Aging and Leukemia

“…In a recent scRNA-seq mapping experiment of large BM hematopoietic cell populations, a small amount of heterogeneous MSCs were captured, with one subset expressing high levels of the key bone marrow-homing cytokine CXCL12. This MSC subclass was later validated by high enrichment of CXCL12 and other key MSC signature genes from FACS-based isolation of CD13 + CD11a− cells ( Triana et al, 2021 ). Another notable exception is a study done by Wang et al (2020) , where a total of 14.494 CD271 + BM-MNCs were analyzed.…”