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

Genes (Basel). 2022 Oct 18;13(10):1890. doi: 10.3390/genes13101890.

Abstract

(1) Background: analyses of gene networks can elucidate hematopoietic differentiation from single-cell gene expression data, but most algorithms generate only a single, static network. Because gene interactions change over time, it is biologically meaningful to examine time-varying structures and to capture dynamic, even transient states, and cell-cell relationships. (2) Methods: a transcriptomic atlas of hematopoietic stem and progenitor cells was used for network analysis. After pseudo-time ordering with Monocle 2, LOGGLE was used to infer time-varying networks and to explore changes of differentiation gene networks over time. A range of network analysis tools were used to examine properties and genes in the inferred networks. (3) Results: shared characteristics of attributes during the evolution of differentiation gene networks showed a "U" shape of network density over time for all three branches for human and mouse. Differentiation appeared as a continuous process, originating from stem cells, through a brief transition state marked by fewer gene interactions, before stabilizing in a progenitor state. Human and mouse shared hub genes in evolutionary networks. (4) Conclusions: the conservation of network dynamics in the hematopoietic systems of mouse and human was reflected by shared hub genes and network topological changes during differentiation.

Keywords: single-cell RNA sequence; time-varying network; transition state during differentiation.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Algorithms
  • Cell Differentiation / genetics
  • Gene Regulatory Networks*
  • Hematopoietic System*
  • Humans
  • Transcriptome / genetics

Grants and funding

This research was supported by National Heart, Lung, and Blood Institute [Intramural Research Program].