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Background <p>Neutrophil differentiation is a well-orchestrated process that involves coordinated changes in the chromatin accessibility, transcription factor (TF) binding, 3D genome-structure and transcription. However, despite significant advances in understanding the later stages of neutrophil maturation, the initial molecular events that trigger and drive the commitment to neutrophil lineage remain poorly characterized, especially the functional roles of master TFs in orchestrating the earliest stages of lineage specification.</p> Results <p>Here, we examine changes in the genome topology, transcriptome, and chromatin accessibility during the neutrophil differentiation process. We demonstrate striking changes in 3D genome structure and chromatin accessibility as early as 4&#xa0;h after all-trans-retinoic acid treatment, which accommodate and regulate gene expression to guide neutrophil lineage differentiation. Analysis of early transcriptional changes confirmed CEBPA as a key TF. To further elucidate the relationships among CEBPA binding, chromatin accessibility, 3D genomic organization, and gene expression, we perform CEBPA HiCut, a technology that simultaneously profiles TF– DNA binding sites and TF-mediated 3D genome interactions. Our first TF-mediated HiCut experiment in neutrophils revealed the synergistic relationship and sequential regulation cascade between this core TF and chromatin accessibility, 3D genomic organization, and gene expression.</p> Conclusions <p>Our work systematically investigates coordinated chromatin accessibility, TF binding, 3D genome-structure and transcriptional changes during neutrophil differentiation, especially at initialization. Our study highlights the sequential interplay between the initial changes of chromatin state, 3D genome organization and pioneer TF s such as CEBPA.</p>

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An integrated multi-omics and network analysis of neutrophil differentiation from initial- to late-stage

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月30日

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  • Qing Chen,
  • Tianchang Yang,
  • Yingping Hou,
  • Kai Wang,
  • Tingting Li,
  • Longteng Wang,
  • Cuiyun Dou,
  • Panpan Cheng,
  • Minglei Shi,
  • Wei Li

摘要

Background

Neutrophil differentiation is a well-orchestrated process that involves coordinated changes in the chromatin accessibility, transcription factor (TF) binding, 3D genome-structure and transcription. However, despite significant advances in understanding the later stages of neutrophil maturation, the initial molecular events that trigger and drive the commitment to neutrophil lineage remain poorly characterized, especially the functional roles of master TFs in orchestrating the earliest stages of lineage specification.

Results

Here, we examine changes in the genome topology, transcriptome, and chromatin accessibility during the neutrophil differentiation process. We demonstrate striking changes in 3D genome structure and chromatin accessibility as early as 4 h after all-trans-retinoic acid treatment, which accommodate and regulate gene expression to guide neutrophil lineage differentiation. Analysis of early transcriptional changes confirmed CEBPA as a key TF. To further elucidate the relationships among CEBPA binding, chromatin accessibility, 3D genomic organization, and gene expression, we perform CEBPA HiCut, a technology that simultaneously profiles TF– DNA binding sites and TF-mediated 3D genome interactions. Our first TF-mediated HiCut experiment in neutrophils revealed the synergistic relationship and sequential regulation cascade between this core TF and chromatin accessibility, 3D genomic organization, and gene expression.

Conclusions

Our work systematically investigates coordinated chromatin accessibility, TF binding, 3D genome-structure and transcriptional changes during neutrophil differentiation, especially at initialization. Our study highlights the sequential interplay between the initial changes of chromatin state, 3D genome organization and pioneer TF s such as CEBPA.