基于生物信息学在单细胞维度解析人胚胎早期发育阶段造血系统的发生及其调控机制  

Dissecting the haematopoiesis and its regulatory mechanisms of the human early embryo in single cell resolution based on bioinformatic analysis

作　　者：朱瑶瑶 刘双庆[1] 刘晓礼 宁莉[1] Yaoyao Zhu;Shuangqing Liu;Xiaoli Liu;Li Ning(Department of Clinical Laboratory,the Second Hospital of Tianjin Medical University,Tianjin 300211,China)

机构地区：[1]天津医科大学第二医院检验科,300211

出　　处：《中华细胞与干细胞杂志（电子版）》2022年第5期266-273,共8页Chinese Journal of Cell and Stem Cell（Electronic Edition）

基　　金：天津医科大学第二医院青年科研基金项目(2021ydey16);天津市卫生健康委员会科技项目(ZC20028);天津医科大学第二医院青年科研基金项目(2019ydey16)。

摘　　要：目的解析人胚胎早期发育阶段造血系统的异质性及其潜在调控机制。方法利用生物信息学方法对早期人胚胎样本来源的单细胞转录组测序数据进行深度分析,包括复杂数据的降维分析、不同细胞亚群的鉴定及其相关性、非造血细胞对造血系统的潜在调控作用以及造血系统本身的发育路径和调控机制的解析;数据可视化由R编程语言、多种R包和Python包完成。结果人早期发育阶段存在多种细胞类型,并且早在卡内基分期(CS)7阶段就已经产生了造血系统;其他细胞类型可通过受配体的介导发挥对造血系统的潜在调控作用;造血的发生伴随着内皮细胞特征的弱化及各种特征性血细胞功能的增强;基于单细胞转录组数据,揭示了人胚胎发育早期造血系统的异质性,并鉴定出多种可能对特定细胞类型发挥作用的调控因子。结论人胚胎早期发育阶段的造血系统存在异质性,造血系统的发生可能受到其他细胞类型的调控,不同类型的血细胞在人胚胎发育早期已经存在对特定谱系具有特定功能的调控因子。ObjectiveTo decode the heterogeneity of human hematopoietic system in early development of human embryo and its potential regulatory mechanisms.MethodsBioinformatic methods were used to explore the single-cell transcriptome sequencing data of the earliest human embryo samples so far, including dimensional reduction analysis, the identification and correlation analysis of different cell subsets, the potential regulation of non-hematopoietic cells on hematopoietic system as well as the development pathway and the regulation mechanism of hematopoietic system itself;data visualization is conducted by R programming language and various R and Python packages.ResultsMany cell types were detected in early human embryonic development, and the hematopoietic system could be was traced as early as CS7 stage;non-hematopoietic cells played potential regulatory roles in hematopoietic system through the receptors-ligands;the development of hematopoiesis was accompanied by the attenuation of endothelial cell characteristics and the enhancement of the functions of specific blood cell types;based on this single-cell transcriptome dataset, the heterogeneity of hematopoietic system in the early stage of human embryonic development was revealed and a variety of regulatory factors that plays a role in specific cell types were identified.ConclusionsHeterogeneitiesof the hematopoietic system in the early human embryo development were identified, and the hematopoietic system may be regulated by other cell types. Potential regulatory factors of specific blood celltypes in this early stage were revealed.

关 键 词：造血系统 单细胞转录组测序 胚胎发育 生物信息学 造血调控 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]