Abstract

High throughput single-cell RNA-seq has been successfully implemented to dissect the cellular and molecular features underlying hematopoiesis. However, an elaborate and comprehensive transcriptome reference of the whole blood system is lacking. Here, we profiled the transcriptomes of 7551 human blood cells representing 32 immunophenotypic cell types, including hematopoietic stem cells, progenitors and mature blood cells derived from 21 healthy donors. With high sequencing depth and coverage, we constructed a single-cell transcriptional atlas of blood cells (ABC) on the basis of both protein-coding genes and long noncoding RNAs (lncRNAs), and showed a high consistence between them. Notably, putative lncRNAs and transcription factors regulating hematopoietic cell differentiation were identified. While common transcription factor regulatory networks were activated in neutrophils and monocytes, lymphoid cells dramatically changed their regulatory networks during differentiation. Furthermore, we showed a subset of nucleated erythrocytes actively expressing immune signals, suggesting the existence of erythroid precursors with immune functions. Finally, a web portal offering transcriptome browsing and blood cell type prediction has been established. Thus, our work provides a transcriptional map of human blood cells at single-cell resolution, thereby offering a comprehensive reference for the exploration of physiological and pathological hematopoiesis.

中文翻译：

---

人类血细胞的单细胞转录组学景观

摘要

高通量单细胞 RNA-seq 已成功用于剖析造血功能的细胞和分子特征。然而，缺乏对全血系统的详尽而全面的转录组参考。在这里，我们分析了代表 32 种免疫表型细胞类型的 7551 个人血细胞的转录组，包括造血干细胞、祖细胞和来自 21 名健康供体的成熟血细胞。凭借高测序深度和覆盖率，我们在蛋白质编码基因和长链非编码RNA（lncRNA）的基础上构建了血细胞单细胞转录图谱（ABC），并显示它们之间的高度一致性。值得注意的是，鉴定了调节造血细胞分化的推定的 lncRNA 和转录因子。虽然常见的转录因子调节网络在中性粒细胞和单核细胞中被激活，但淋巴细胞在分化过程中显着改变了它们的调节网络。此外，我们展示了一部分有核红细胞积极表达免疫信号，表明存在具有免疫功能的红细胞前体。最后，建立了一个提供转录组浏览和血细胞类型预测的门户网站。因此，我们的工作以单细胞分辨率提供了人类血细胞的转录图谱，从而为探索生理和病理造血提供了全面的参考。我们展示了一部分有核红细胞积极表达免疫信号，表明存在具有免疫功能的红细胞前体。最后，建立了一个提供转录组浏览和血细胞类型预测的门户网站。因此，我们的工作以单细胞分辨率提供了人类血细胞的转录图谱，从而为探索生理和病理造血提供了全面的参考。我们展示了一部分有核红细胞积极表达免疫信号，表明存在具有免疫功能的红细胞前体。最后，建立了一个提供转录组浏览和血细胞类型预测的门户网站。因此，我们的工作以单细胞分辨率提供了人类血细胞的转录图谱，从而为探索生理和病理造血提供了全面的参考。