An immunophenotype-coupled transcriptomic atlas of human hematopoietic progenitors.

Autor: Zhang X; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA., Song B; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.; Immunology Graduate Program, University of Cincinnati, Cincinnati, OH, USA., Carlino MJ; Yale Stem Cell Center, Yale School of Medicine, New Haven, CT, USA.; Department of Laboratory Medicine, Yale University, New Haven, CT, USA., Li G; Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA., Ferchen K; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA., Chen M; Yale Stem Cell Center, Yale School of Medicine, New Haven, CT, USA.; Department of Laboratory Medicine, Yale University, New Haven, CT, USA., Thompson EN; Yale Stem Cell Center, Yale School of Medicine, New Haven, CT, USA.; Department of Laboratory Medicine, Yale University, New Haven, CT, USA.; Department of Cell Biology, Yale School of Medicine, New Haven, CT, USA., Kain BN; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA., Schnell D; Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA., Thakkar K; Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA., Kouril M; Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA., Jin K; Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA., Hay SB; Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA., Sen S; Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA., Bernardicius D; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA., Ma S; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA., Bennett SN; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA., Croteau J; BioLegend, Inc., San Diego, CA, USA., Salvatori O; BioLegend, Inc., San Diego, CA, USA., Lye MH; Curiox Biosystems, Inc., Woburn, MA, USA., Gillen AE; Division of Hematology, University of Colorado School of Medicine, Aurora, CO, USA.; Rocky Mountain Regional VA Medical Center, Aurora, CO, USA., Jordan CT; Division of Hematology, University of Colorado School of Medicine, Aurora, CO, USA., Singh H; Departments of Immunology and Computational and Systems Biology, Center for Systems Immunology, University of Pittsburgh, Pittsburgh, PA, USA., Krause DS; Yale Stem Cell Center, Yale School of Medicine, New Haven, CT, USA.; Department of Laboratory Medicine, Yale University, New Haven, CT, USA.; Department of Cell Biology, Yale School of Medicine, New Haven, CT, USA., Salomonis N; Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. nathan.salomonis@cchmc.org.; Department of Pediatrics, University of Cincinnati, Cincinnati, OH, USA. nathan.salomonis@cchmc.org., Grimes HL; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. lee.grimes@cchmc.org.; Department of Pediatrics, University of Cincinnati, Cincinnati, OH, USA. lee.grimes@cchmc.org.; Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. lee.grimes@cchmc.org.
Jazyk: angličtina
Zdroj: Nature immunology [Nat Immunol] 2024 Apr; Vol. 25 (4), pp. 703-715. Date of Electronic Publication: 2024 Mar 21.
DOI: 10.1038/s41590-024-01782-4
Abstrakt: Analysis of the human hematopoietic progenitor compartment is being transformed by single-cell multimodal approaches. Cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) enables coupled surface protein and transcriptome profiling, thereby revealing genomic programs underlying progenitor states. To perform CITE-seq systematically on primary human bone marrow cells, we used titrations with 266 CITE-seq antibodies (antibody-derived tags) and machine learning to optimize a panel of 132 antibodies. Multimodal analysis resolved >80 stem, progenitor, immune, stromal and transitional cells defined by distinctive surface markers and transcriptomes. This dataset enables flow cytometry solutions for in silico-predicted cell states and identifies dozens of cell surface markers consistently detected across donors spanning race and sex. Finally, aligning annotations from this atlas, we nominate normal marrow equivalents for acute myeloid leukemia stem cell populations that differ in clinical response. This atlas serves as an advanced digital resource for hematopoietic progenitor analyses in human health and disease.
(© 2024. The Author(s).)
Databáze: MEDLINE
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