Comparative Transcriptomic Analysis of the Hematopoietic System between Human and Mouse by Single Cell RNA Sequencing

Abstract

(1) Background: mouse models are fundamental to the study of hematopoiesis, but comparisons between mouse and human in single cells have been limited in depth. (2) Methods: we constructed a single-cell resolution transcriptomic atlas of hematopoietic stem and progenitor cells (HSPCs) of human and mouse, from a total of 32,805 single cells. We used Monocle to examine the trajectories of hematopoietic differentiation, and SCENIC to analyze gene networks underlying hematopoiesis. (3) Results: After alignment with Seurat 2, the cells of mouse and human could be separated by same cell type categories. Cells were grouped into 17 subpopulations; cluster-specific genes were species-conserved and shared functional themes. The clustering dendrogram indicated that cell types were highly conserved between human and mouse. A visualization of the Monocle results provided an intuitive representation of HSPC differentiation to three dominant branches (Erythroid/megakaryocytic, Myeloid, and Lymphoid), derived directly from the hematopoietic stem cell and the long-term hematopoietic stem cells in both human and mouse. Gene regulation was similarly conserved, reflected by comparable transcriptional factors and regulatory sequence motifs in subpopulations of cells. (4) Conclusions: our analysis has confirmed evolutionary conservation in the hematopoietic systems of mouse and human, extending to cell types, gene expression and regulatory elements.

Single-Cell RNA Sequencing: Opportunities and Challenges for Studies on Corneal Biology in Health and Disease

“…We chose to focus on single-cell studies of the human cornea, rather than from other model organisms [ 36 , 37 , 38 ], because human cornea data are directly relevant for regenerative medicine. In addition, how cell types in the cornea are conserved between different organisms is not yet fully clear [ 39 , 40 , 41 ].…”

“…We chose to focus on single-cell studies of the human cornea, rather than from other model organisms [36][37][38], because human cornea data are directly relevant for regenerative medicine. In addition, how cell types in the cornea are conserved between different organisms is not yet fully clear [39][40][41]. During embryonic development, the cornea undergoes a series of intricate molecular and cellular events to form its distinct structure.…”

Time-Varying Gene Expression Network Analysis Reveals Conserved Transition States in Hematopoietic Differentiation between Human and Mouse

“…The temporal dynamics of this intergenic interaction during hematopoietic differentiation are yet to be delineated. Gaussian Graphic Models (GGMs) have been successfully applied to time-series data to estimate time-varying graphs, on the assumption that covariance matrices change smoothly over time [ 9 , 10 , 11 , 12 , 13 ]. Thus a series of networks across time facilitate understanding of the evolution of gene interactions.…”

Cutting-Edge Methods for Better Understanding Cells

“…They used a number of scRNA-seq analysis tools, such as Monocle, Seurat 2 and SCENIC, to analyze the data. Through conducting a comparison, they identified conserved HSPC types, conserved cell-type expression profiles and conserved cell-type-specific regulatory elements, motifs and networks [ 4 ]. For the validation of scRNA-seq results, Zucha et al provided a step-by-step tutorial of a reverse transcription quantitative PCR (RT-qPCR), which could also be used for efficient screening prior to scRNA-Seq experiments.…”