Comprehensive analysis of single-cell RNA sequencing data from healthy human marrow hematopoietic cells

BMC Research Notes

Xingmin Feng¹  Xin Zhao¹  Qingguo Liu¹  Sachiko Kajigaya¹  Neal S. Young¹  Shouguo Gao¹  Zhijie Wu¹  Fengkui Zhang² 

[1] Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health;State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College;

关键词: Single cell RNA-sequencing;    Hematopoiesis;    Differentiation;    Quiescence of stem cell;   

DOI  :  10.1186/s13104-020-05357-y

来源: DOAJ

【 摘 要 】

Abstract Objective Single cell methodology enables detection and quantification of transcriptional changes and unravelling dynamic aspects of the transcriptional heterogeneity not accessible using bulk sequencing approaches. We have applied single-cell RNA-sequencing (scRNA-seq) to fresh human bone marrow CD34+ cells and profiled 391 single hematopoietic stem/progenitor cells (HSPCs) from healthy donors to characterize lineage- and stage-specific transcription during hematopoiesis. Results Cells clustered into six distinct groups, which could be assigned to known HSPC subpopulations based on lineage specific genes. Reconstruction of differentiation trajectories in single cells revealed four committed lineages derived from HSCs, as well as dynamic expression changes underlying cell fate during early erythroid-megakaryocytic, lymphoid, and granulocyte-monocyte differentiation. A similar non-hierarchical pattern of hematopoiesis could be derived from analysis of published single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq), consistent with a sequential relationship between chromatin dynamics and regulation of gene expression during lineage commitment (first, altered chromatin conformation, then mRNA transcription). Computationally, we have reconstructed molecular trajectories connecting HSCs directly to four hematopoietic lineages. Integration of long noncoding RNA (lncRNA) expression from the same cells demonstrated mRNA transcriptome, lncRNA, and the epigenome were highly homologous in their pattern of gene activation and suppression during hematopoietic cell differentiation.

【 授权许可】

Unknown