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Transcriptomic characterisation of haematopoietic stem and progenitor cells from human adult bone marrow, spleen and peripheral blood

ABSTRACT: Haematopoietic stem and progenitor cells (HSPCs), the precursors of all blood cells, reside predominantly in the bone marrow (BM). Recent evidence suggests that other anatomical sites may contribute significantly to blood production, but the cellular, molecular and functional composition of extramedullary HSPC pools remains unexplored. Here, we comprehensively characterized the single-cell composition of the adult human HSPC pool within matched BM, spleen and peripheral blood (PB) from four healthy organ donors. 10x scRNA-seq of >65,000 HSPCs from all three sites defined transcriptionally distinct cell clusters that correspond to precursors of all haematopoietic lineages but also stem cells (HSCs). We find that, contrary to actively proliferating BM HSPCs, extramedullary tissues are enriched for low-to-non proliferating early progenitors, indicative of no significant haematopoiesis in these tissues at steady-state. We further describe a shared transcriptional signature of haematopoietic stem cells and multipotent progenitors (HSC/MPPs) at extramedullary sites and the increased abundance of lineage-primed subsets, that distinguishes them from BM HSC/MPPs. This dataset is part of the Human Cell Atlas.

ORGANISM(S): Homo sapiens

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PROVIDER: S-SUBS4 | biostudies-other |

SECONDARY ACCESSION(S): PRJEB36885

REPOSITORIES: biostudies-other

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Project description:BACKGROUND:Randomized trials have shown that the transplantation of filgrastim-mobilized peripheral-blood stem cells from HLA-identical siblings accelerates engraftment but increases the risks of acute and chronic graft-versus-host disease (GVHD), as compared with the transplantation of bone marrow. Some studies have also shown that peripheral-blood stem cells are associated with a decreased rate of relapse and improved survival among recipients with high-risk leukemia. METHODS:We conducted a phase 3, multicenter, randomized trial of transplantation of peripheral-blood stem cells versus bone marrow from unrelated donors to compare 2-year survival probabilities with the use of an intention-to-treat analysis. Between March 2004 and September 2009, we enrolled 551 patients at 48 centers. Patients were randomly assigned in a 1:1 ratio to peripheral-blood stem-cell or bone marrow transplantation, stratified according to transplantation center and disease risk. The median follow-up of surviving patients was 36 months (interquartile range, 30 to 37). RESULTS:The overall survival rate at 2 years in the peripheral-blood group was 51% (95% confidence interval [CI], 45 to 57), as compared with 46% (95% CI, 40 to 52) in the bone marrow group (P=0.29), with an absolute difference of 5 percentage points (95% CI, -3 to 14). The overall incidence of graft failure in the peripheral-blood group was 3% (95% CI, 1 to 5), versus 9% (95% CI, 6 to 13) in the bone marrow group (P=0.002). The incidence of chronic GVHD at 2 years in the peripheral-blood group was 53% (95% CI, 45 to 61), as compared with 41% (95% CI, 34 to 48) in the bone marrow group (P=0.01). There were no significant between-group differences in the incidence of acute GVHD or relapse. CONCLUSIONS:We did not detect significant survival differences between peripheral-blood stem-cell and bone marrow transplantation from unrelated donors. Exploratory analyses of secondary end points indicated that peripheral-blood stem cells may reduce the risk of graft failure, whereas bone marrow may reduce the risk of chronic GVHD. (Funded by the National Heart, Lung, and Blood Institute-National Cancer Institute and others; ClinicalTrials.gov number, NCT00075816.).

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Transcriptomic characterisation of haematopoietic stem and progenitor cells from human adult bone marrow, spleen and peripheral blood

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