Hongpeng Wang , Minghua Li

Biotechnology Research Center, Cuixi Academy of Biotechnology, Zhuji, 311800, China
Author    Correspondence author
Computational Molecular Biology, 2025, Vol. 15, No. 2   
Received: 01 Jan., 2025    Accepted: 12 Mar., 2025    Published: 01 Apr., 2025

This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Single-cell RNA sequencing (scRNA-seq) and single-cell chromatin accessibility sequencing (scATAC-seq) are important technological breakthroughs in the field of life sciences in recent years, providing an unprecedented high-resolution perspective for studying the mechanism of cell fate determination. The gene expression profile of individual cells can be analyzed through scRNA-seq, revealing cellular heterogeneity and developmental trajectories. scATAC-seq can detect the chromatin open state at the single-cell level and identify potential regulatory elements and binding sites of transcription factors. The integration and analysis of scRNA-seq and scATAC-seq data can simultaneously characterize the cell state at both the transcriptional and epigenetic levels, thereby gaining an in-depth understanding of the synergistic role of transcriptional regulatory networks and chromatin dynamics in the process of cell fate determination. This study will review the principles and applications of single-cell omics technology, discuss the roles of transcription factors and chromatin accessibility in cell fate determination, and focus on introducing the key regulatory factors, cis-regulatory elements and gene regulatory networks revealed by the integrated analysis of scRNA-seq and scATAC-seq. We will also introduce methods for inferring cell fate trajectories and conducting pathway enrichment analysis using integrated data, and through cases of hematopoietic and nervous system development, illustrate how integrated analysis can reveal new insights into the process of cell differentiation. Finally, the potential clinical application value of single-cell multi-omics in areas such as tumor heterogeneity, immune cell fate, and regenerative medicine is prospected. The limitations of current technologies and analytical methods are analyzed, and the future development directions are prospected.

Single-cell sequencing; Chromatin accessibility; Transcriptomics; Multi-omics integration; Cell fate determination