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Peer-reviewedCC BYGenes & diseases

Mapping intestinal microenvironment heterogeneity in Hirschsprung's disease by spatial transcriptomics: Role of THBS1 in macrophage polarization and neural stem cell regulation.

  • Jinxin Li1,2,3
  • Junbao Du2,3,4
  • Lian Hou1,2,3
  • Qing Luo2
  • Quan Kang1,2
4 affiliations
  1. 1Department of General Surgery and Trauma, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
  2. 2Stem Cell Biology and Therapy Laboratory, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
  3. 3Stem Cell Biology and Therapy Laboratory, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
  4. 4The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310002, China.
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Abstract

The pathogenic role of the intestinal microenvironment on Hirschsprung's disease (HSCR) is increasingly recognized; however, the spatial expression patterns and underlying molecular mechanisms of the HSCR intestinal microenvironment remain unclear. In this study, we generated the first comprehensive spatial transcriptomic map of HSCR and revealed microenvironmental heterogeneity. Spatial transcriptomics revealed THBS1 as a consistently down-regulated gene in HSCR aganglionic segments. In vitro experiments using THP-1 and SH-SY5Y cells showed that THBS1 promoted M2-like polarization and interacted with SDC1. Furthermore, THBS1-overexpressing macrophages enhanced the proliferation and migration of SH-SY5Y cells in co-culture. These findings suggest a potential role for THBS1 in modulating macrophage-neural interactions in the HSCR microenvironment, though further validation in primary cells is needed.

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Cite

BibTeXRIS
BibTeX
@article{li2026mapping,
  title = {{Mapping intestinal microenvironment heterogeneity in Hirschsprung's disease by spatial transcriptomics: Role of THBS1 in macrophage polarization and neural stem cell regulation.}},
  author = {Jinxin Li and Junbao Du and Lian Hou and Qing Luo and Quan Kang},
  journal = {Genes \& diseases},
  year = {2026},
  month = may,
  doi = {10.1016/j.gendis.2026.102254},
  url = {https://europepmc.org/article/MED/42926789},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Mapping intestinal microenvironment heterogeneity in Hirschsprung's disease by spatial transcriptomics: Role of THBS1 in macrophage polarization and neural stem cell regulation.
AU  - Jinxin Li
AU  - Junbao Du
AU  - Lian Hou
AU  - Qing Luo
AU  - Quan Kang
PY  - 2026
DA  - 2026/05/26
JO  - Genes & diseases
DO  - 10.1016/j.gendis.2026.102254
UR  - https://europepmc.org/article/MED/42926789
AB  - The pathogenic role of the intestinal microenvironment on Hirschsprung's disease (HSCR) is increasingly recognized; however, the spatial expression patterns and underlying molecular mechanisms of the HSCR intestinal microenvironment remain unclear. In this study, we generated the first comprehensive spatial transcriptomic map of HSCR and revealed microenvironmental heterogeneity. Spatial transcriptomics revealed THBS1 as a consistently down-regulated gene in HSCR aganglionic segments. In vitro experiments using THP-1 and SH-SY5Y cells showed that THBS1 promoted M2-like polarization and interacted with SDC1. Furthermore, THBS1-overexpressing macrophages enhanced the proliferation and migration of SH-SY5Y cells in co-culture. These findings suggest a potential role for THBS1 in modulating macrophage-neural interactions in the HSCR microenvironment, though further validation in primary cells is needed.
SN  - 2352-4820
SN  - 2352-3042
ER  -