Single‐Cell Chromatin Accessibility Analysis Reveals Subgroup‐Specific TF‐NTR Regulatory Circuits in Medulloblastoma

Abstract: Medulloblastoma (MB) stands as one of the prevalent malignant brain tumors among pediatric patients. Despite its prevalence, the intricate interplay between the regulatory program driving malignancy in MB cells and their interactions with the microenvironment remains insufficiently understood. Leveraging the capabilities of single‐cell Assay for Transposase‐Accessible Chromatin sequencing (scATAC‐seq), the chromatin accessibility landscape is unveiled across 59,015 distinct MB cells. This expansive dataset encompasses cells belonging to discrete molecular subgroups, namely SHH, WNT, Group3, and Group4. Within these chromatin accessibility profiles, specific regulatory elements tied to individual subgroups are uncovered, shedding light on the distinct activities of transcription factors (TFs) that likely orchestrate the tumorigenesis process. Moreover, it is found that certain neurotransmitter receptors (NTRs) are subgroup‐specific and can predict MB subgroup classification when combined with their associated transcription factors. Notably, targeting essential NTRs within tumors influences both the in vitro sphere‐forming capability and the in vivo tumorigenic capacity of MB cells. These findings collectively provide fresh insights into comprehending the regulatory networks and cellular dynamics within MBs. Furthermore, the significance of the TF‐NTR regulatory circuits is underscored as prospective biomarkers and viable therapeutic targets.

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch

Bibliographic citation
Single‐Cell Chromatin Accessibility Analysis Reveals Subgroup‐Specific TF‐NTR Regulatory Circuits in Medulloblastoma ; day:17 ; month:06 ; year:2024 ; extent:17
Advanced science ; (17.06.2024) (gesamt 17)

Creator
Gao, Xiaoyue
Zhuang, Qiyuan
Li, Yun
Li, Guochao
Huang, Zheng
Chen, Shenzhi
Sun, Shaoxing
Yang, Hui
Jiang, Lan
Mao, Ying

DOI
10.1002/advs.202309554
URN
urn:nbn:de:101:1-2406171429351.897734066460
Rights
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Last update
14.08.2025, 10:45 AM CEST

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Associated

  • Gao, Xiaoyue
  • Zhuang, Qiyuan
  • Li, Yun
  • Li, Guochao
  • Huang, Zheng
  • Chen, Shenzhi
  • Sun, Shaoxing
  • Yang, Hui
  • Jiang, Lan
  • Mao, Ying

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