美国辛辛那提儿童医院医疗中心Grimes, H. Leighton小组报道了人类造血祖细胞的免疫表型偶联转录组图谱。2024年3月21日出版的《自然—免疫学》发表了这项成果。

为了系统地对人原代骨髓细胞进行转录组和表位的测序，研究组使用266种转录组和表位测序抗体(抗体来源标签)进行滴定，并使用机器学习优化132种抗体。多模态分析解析了80个由不同表面标记和转录组定义的干细胞、祖细胞、免疫细胞、基质细胞和过渡细胞。

该数据集使流式细胞术解决方案能够在硅预测细胞状态，并确定跨越种族和性别的供体一致检测到的数十个细胞表面标记。最后，通过比对该图谱的注释，课题组为急性髓性白血病干细胞群指定了在临床反应上不同的正常骨髓等同物。该图谱是人类健康和疾病中造血祖细胞分析的先进数字资源。

据悉，人类造血祖细胞室的分析正被单细胞多模态方法所改变。通过测序(CITE-seq)对转录组和表位进行细胞索引，可以实现表面蛋白和转录组的偶联分析，从而揭示祖细胞状态下的基因组程序。

附：英文原文

Title: An immunophenotype-coupled transcriptomic atlas of human hematopoietic progenitors

Author: Zhang, Xuan, Song, Baobao, Carlino, Maximillian J., Li, Guangyuan, Ferchen, Kyle, Chen, Mi, Thompson, Evrett N., Kain, Bailee N., Schnell, Dan, Thakkar, Kairavee, Kouril, Michal, Jin, Kang, Hay, Stuart B., Sen, Sidharth, Bernardicius, David, Ma, Siyuan, Bennett, Sierra N., Croteau, Josh, Salvatori, Ornella, Lye, Melvin H., Gillen, Austin E., Jordan, Craig T., Singh, Harinder, Krause, Diane S., Salomonis, Nathan, Grimes, H. Leighton

Issue&Volume: 2024-03-21

Abstract: 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.

DOI: 10.1038/s41590-024-01782-4

Source: https://www.nature.com/articles/s41590-024-01782-4