基于单细胞转录组测序分析描绘人类早期胚胎红细胞发育图谱

Single-cell RNA sequencing based analysis depicts the development map of human early embryonic erythrocytes

目的利用单细胞转录组测序(scRNA-seq)在单细胞水平系统描绘人早期红系发育的细胞图谱及分子轨迹。方法通过对人妊娠第36天CS15后期的胚胎卵黄囊组织scRNA-seq数据进行主成分分析(PCA);聚类分析以及拟时序分析;观察标记基因在不同细胞群体中的表达情况;预测红系细胞发生时间和发育路径。结果在CS15的卵黄囊的不同细胞群体中,红细胞及其祖细胞、前体细胞等的标记基因存在差异性表达,不同细胞的发生时序不同,且卵黄囊内的红细胞存在一定的异质性。CS15的卵黄囊内存在类型丰富的细胞,可能包括血管内皮细胞、造血前体细胞、粒细胞、不同状态的红细胞以及单核细胞等。结论推测人早期红系发育路径大致为血管内皮细胞分化产生造血前体细胞,进一步分化成为红髓祖细胞,最终产生巨核细胞和红细胞。

Objective Single-cell RNA sequencing(scRNA-seq)was used to systematically delineate the cell atlas and molecular tracks of human early erythroid development at the single-cell level.Methods The dataset of scRNA-seq of human embryo yolk sac at CS15 stage was analyzed by principal component analysis(PCA),cluster analysis and pseudostime analysis to observe the expression of marker genes in different cell clusters,and to predict the occurrence time and development path of erythroid.Results In different cell clusters of yolk sac at CS15 stage,marker genes of erythrocytes and progenitor cells were differentially expressed.The occurrence time of various cells was different,and there was some heterogeneity in erythrocytes in the yolk sac.There were abundant types of cells in the yolk sac at CS15 stage,which could include vascular endothelial cells,hematopoietic progenitor cells,granulocytes,different status of red blood cells and monocytes.Conclusions It is speculated that early development path of human erythroid is as follows:vascular endothelial cells differentiate into hematopoietic progenitor cells,further differentiate into red myeloid progenitor cells,and finally produce megakaryocytes and erythrocytes.