2. Academic Validation
  3. Single-cell landscape of the cellular microenvironment in three different colonic polyp subtypes in children

Single-cell landscape of the cellular microenvironment in three different colonic polyp subtypes in children

  • Clin Transl Med. 2024 Jan;14(1):e1535. doi: 10.1002/ctm2.1535.
Yafei Deng 1 2,  Canlin Li 3,  Lanlan Huang 1 2,  Peiwen Xiong 1,  Yana Li 1,  Yongjie Liu 1,  Songyang Li 1,  Weijian Chen 4,  Qiang Yin 5,  Yong Li 5,  Qinglan Yang 1,  Hongyan Peng 1,  Shuting Wu 1,  Xiangyu Wang 1,  Qin Tong 2 3,  Hongjuan Ouyang 3,  Die Hu 6,  Xinjia Liu 1 2,  Liping Li 1,  Jieyu You 3,  Zhiyi Sun 7,  Xiulan Lu 1,  Zhenghui Xiao 1,  Youcai Deng 6,  Hongmei Zhao 3
Affiliations

Affiliations

  • 1 Pediatrics Research Institute of Hunan Province and Hunan Provincial Key Laboratory of Children's Emergency Medicine, Hunan Children's Hospital, Changsha, China.
  • 2 The School of Pediatrics, Hengyang Medical School, University of South China, Changsha, China.
  • 3 Department of Digestive Nutrition, Hunan Children's Hospital, Changsha, China.
  • 4 Department of Pathology, Hunan Children's Hospital, Changsha, China.
  • 5 Department of Pediatric Surgery, Hunan Children's Hospital, Changsha, China.
  • 6 Department of Clinical Hematology, College of Pharmacy and Laboratory Medicine Science, Army Medical University, Chongqing, China.
  • 7 Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, Michigan, USA.
PMID: 38264936 DOI: 10.1002/ctm2.1535
Abstract

Background: The understanding of the heterogeneous cellular microenvironment of colonic polyps in paediatric patients with solitary juvenile polyps (SJPs), polyposis syndrome (PJS) and Peutz-Jeghers syndrome (PJS) remains limited.

Methods: We conducted single-cell RNA Sequencing and multiplexed immunohistochemistry (mIHC) analyses on both normal colonic tissue and different types of colonic polyps obtained from paediatric patients.

Results: We identified both shared and disease-specific cell subsets and expression patterns that played important roles in shaping the unique cellular microenvironments observed in each polyp subtype. As such, increased myeloid, endothelial and epithelial cells were the most prominent features of SJP, JPS and PJS polyps, respectively. Noticeably, memory B cells were increased, and a cluster of epithelial-mesenchymal transition (EMT)-like colonocytes existed across all polyp subtypes. Abundant neutrophil infiltration was observed in SJP polyps, while CX3CR1hi CD8+ T cells and regulatory T cells (Tregs) were predominant in SJP and JPS polyps, while GZMAhi natural killer T cells were predominant in PJS polyps. Compared with normal colonic tissues, myeloid cells exhibited specific induction of genes involved in chemotaxis and interferon-related pathways in SJP polyps, whereas fibroblasts in JPS polyps had upregulation of myofiber-associated genes and epithelial cells in PJS polyps exhibited induction of a series of nutrient absorption-related genes. In addition, the TNF-α response was uniformly upregulated in most cell subsets across all polyp subtypes, while endothelial cells and fibroblasts separately showed upregulated cell adhesion and EMT signalling in SJP and JPS polyps. Cell-cell interaction network analysis showed markedly enhanced intercellular communication, such as TNF, VEGF, CXCL and collagen signalling networks, among most cell subsets in polyps, especially SJP and JPS polyps.

Conclusion: These findings strengthen our understanding of the heterogeneous cellular microenvironment of polyp subtypes and identify potential therapeutic approaches to reduce the recurrence of polyps in children.

Keywords

cellular microenvironment; epithelial-mesenchymal transition; paediatric colonic polyps; scRNA-seq.

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