造血系统主要起源于hematopoietic stem/progenitor cells (HSPCs)，造血异常可引起多种血液疾病。对造血系统的全面系统评估有助于我们对造血稳态和血液疾病的发展有更深入的理解。
血细胞的分化
这一篇是20年八月发表在Natl Sci Rev (IF: 23.178) 上的文章，对正常人的外周血细胞进行了系统评估。
是一个图谱类文章。在需要的时候，数据可以拿来进行二次分析和挖掘。
这篇文献使用的单细胞技术是STRT-seq，可以参考：单细胞转录组技术简史。
1. Human hematopoietic transcriptome reference
Fig 1a：作者对21个正常人的外周血和骨髓进行了流式分选，得到了32个细胞类型，使用STRT-seq进行了单细胞测序。
Fig 1b：32种(7类)细胞的基因数
Fig 1c：和已发表的10x数据集相比，STRT-seq检测到的基因数和转录本数目比10x显著要高。
Fig 1d：7类细胞的分化轨迹UMAP图提示以HSPC为起始，向其他细胞分化的过程。
Fig 1e：7类细胞的marker基因展示
2. Regulatory networks underlie hematopoietic differentiation
为了进一步探究转录调控过程，作者使用SCENIC进行了转录因子预测
Fig 2a：使用预测的转录因子构建了regulatory atlas of human blood cells。使用转录因子构建的分化轨迹和使用基因构建的轨迹没有很大差别。
Fig 2b：基于转录因子的聚类，得到20个cluster。
Fig 2c：每个细胞群的主要转录因子。Remarkably, monocytes and neutrophils shared the majority of regulons unique to myeloid lineage, while lymphocytes were preferentially regu- lated by cell type specific sub-networks highlighted by the regulon shifts during B cell maturation.
Fig 2d：通过和已报道的转录因子对比，作者鉴定出23个新的转录因子。为了进一步探究这些转录因子的功能，作者做了GO功能富集。结果显示BBX, REL, CREM, CREB3L2 和 GLIS1 与淋巴细胞激活/分化有关；RXRA, STAT2, STAT6, TFF3, TFEC, EGR3, OLIG2, VDR, VENTX 和 ZXDA主要靶向中性粒/粒细胞相关基因；
Additionally, the enriched sequences on the promoter region of target genes for transcription factors like CREM, (TFF3 and NFIX，在附件) were consistent with their annotated motifs, suggesting that these newly identified transcription factors might regulate hematopoiesis in cooperating with canonical networks
3. Landscapes of long non-coding RNAs
lncRNAs play crucial roles in hematopoietic differentiation and development. However, the expression spectrum of lncRNAs in hematopoietic cells at single-cell resolution has not been reported.
因此作者根据lncRNAs构建了7192个血细胞的转录图谱。通过NONCODE database的注释，32种血细胞一共检测到超过1700 lncRNAs。
Fig 3a：造血细胞和单核细胞检测到的lnc较多，NK, T, 中性粒细胞检测到的lnc则较少。（和前面Fig 1b检测到的基因数相一致）
Fig 3b：使用lncRNA构建的分化轨迹和前面使用protein- coding genes构建的轨迹是一致的。
Fig 3c：各个细胞的差异性lncRNAs 和 protein-coding genes具有高度一致性
Fig 3d：随后作者每个细胞群的signature protein-coding genes 和 lncRNAs。We found that signature lncRNAs tended to associate with their adjacent signature protein-coding genes for more differentiated cell types, in contrast to progenitors.
Fig 3e, f：Signature lncRNAs showed higher PhastCons conservation scores (from UCSC 100-way) and higher cell specificity (based on Jensen-Shannon Diver- gence, JSD) compared to background estimations (P values <2.2e−16, Wilcoxon test), suggesting their potential functional roles.
Fig 3g：lncRNAs (NONHSAG031143.2, NONHSAG073805.1, NONHSAG069091.1, NONHSAG108638.1, NONHSAG008235.2 and NONHSAG103763.2) adjacent to hematopoietic signatures (AVP, CD79B, GZMH, CCR7, SPI1 and GATA1) were specifically highly expressed in HSPCs, B cells, NK cells, T cells, neutrophil/monocytes and erythrocytes, respectively.
这么看，lncRNA也是可以作为细胞类型的marker基因的
Altogether, lncRNAs specifically expressed in hematopoietic cells were identified at the single-cell level, and they tended to co-express with their adjacent signature protein-coding genes for more differentiated cells.
4. Elaborate atlas for each hematopoietic cell population
随后作者分别对各个分化谱系做了轨迹分析
5. A web portal for expression data browsing and blood cell type prediction
最后作者建立了一个网站：single-cell transcriptome data of human blood cells
网友评论