The application of single-cell sequencing in the study of the microenvironment and metastasis and recurrence of medulloblastoma

doi:10.3877/cma.j.issn.2095-1221.2026.01.004

Abstract

Abstract:

Medulloblastoma (MB) is the most common malignant brain tumor in children. Currently, the conventional clinical treatments mainly include surgical resection, radiotherapy and chemotherapy. However, the heterogeneity of tumor cells and their interaction with complex microenvironments significantly increase the difficulty of precise treatment, leading to limited efficacy of traditional intervention methods and great challenges for patient prognosis. In recent years, the breakthrough development of single-cell RNA sequencing (scRNA-seq) technology has provided high-resolution research tools for understanding the biological mechanism of MB and the selection of therapeutic targets. This technology reveals the heterogeneous lineage characteristics and the dynamic evolution patterns of the microenvironment of MB tumor cell subtypes at the single-cell level through single-cell gene expression profiling analysis. This article systematically reviews the latest research progress of scRNA-seq in the heterogeneity of MB and the characteristics of the microenvironment, and explores the significance of these findings for understanding the biological mechanism of MB and its potential application value in clinical treatment. Meanwhile, in view of the challenges faced by scRNA-seq, such as the capture efficiency of tumor sample heterogeneity and the integration analysis of spatial transcriptomes, this review proposes its future research directions and application potential for the precise diagnosis and treatment of MB.

Key words: Single-cell RNA sequencing, Medulloblastoma, Tumor heterogeneity, Tumor microenvironment

Jiayu Gao, Huanlei Zhang, Fabin Han. The application of single-cell sequencing in the study of the microenvironment and metastasis and recurrence of medulloblastoma[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2026, 16(01): 31-38.

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References 89

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亚群	WNT	SHH	G3	G4
病例占比（%）	10	30	25	35
诊断高峰期	6 ~ 10岁	婴儿和成人	3 ~ 5岁	成人
性别比例（男:女）	1 : 1	1 : 1	2 : 1	3 : 1
预后	很好	TP53野生型良好；TP53突变型较差	很差	良好
细胞起源	苔藓纤维神经元细胞	颗粒神经元祖细胞	菱唇脑室下区祖细胞	菱唇脑室下区祖细胞
突变基因	CTNNB1、DDX3X、SMARCA4、TP53	TERT、PTCH1、TP53、SUFU、SMO	MYC、GLI1B、GFI1、OTX2、SMARCA4	MYCN、CDK6、KDM6A

亚群	WNT	SHH	G3	G4
病例占比（%）	10	30	25	35
诊断高峰期	6 ~ 10岁	婴儿和成人	3 ~ 5岁	成人
性别比例（男:女）	1 : 1	1 : 1	2 : 1	3 : 1
预后	很好	TP53野生型良好；TP53突变型较差	很差	良好
细胞起源	苔藓纤维神经元细胞	颗粒神经元祖细胞	菱唇脑室下区祖细胞	菱唇脑室下区祖细胞
突变基因	CTNNB1、DDX3X、SMARCA4、TP53	TERT、PTCH1、TP53、SUFU、SMO	MYC、GLI1B、GFI1、OTX2、SMARCA4	MYCN、CDK6、KDM6A

TME细胞	作用	治疗靶点	参考文献
TILs	CD8⁺ CTL通过抗原特异性识别直接介导肿瘤细胞杀伤；CD4⁺ Th通过分泌细胞因子促进适应性免疫反应；Tregs抑制抗肿瘤免疫反应，促进肿瘤进展。	GZMA	[33,34]
	Tregs通过释放抗炎细胞因子来控制免疫细胞的活性。		[36,37]
TAMs	M2型TAMs由IL-4诱导释放生长因子，参与肿瘤进展和免疫抑制。	SPP1、CEBPB、OLFML2B、CD1C、NAT1	[42,43]
	TAMs浸润水平较低与复发率和远处转移风险的下降相关。		[52]
	M1型TAMs预示着更好的无进展生存期。		[3,37,53]
TAAs	TAAs通过分泌细胞因子、生长因子及上调肿瘤细胞生存基因的表达，促进脑肿瘤生长和进展。	HMGB1、PTPRZ1	[56,59]
	TAAs通过提供SHH配体激活Ptch1介导的非经典的SHH通路，诱导肿瘤细胞Nestin表达并解除Gli3对经典SHH信号通路的抑制，从而驱动肿瘤的起始与维持。		[56,60,61]
	坏死性TAAs分泌CCL2，激活JAK2/STAT3-Notch通路，维持转移性MB干细胞特性并驱动肿瘤进展。		[66]
	在复发性SHH-MB中，肿瘤细胞可以在BMPs刺激下转分化为TAAs，促进肿瘤进展。		[66,67]
TAFs	PDGF配体趋化性招募TAFs，并将其重编程为转移相关TAFs，通过分泌BMP等因子，增强MB在软脑膜的定植能力和转移灶生长。	PDGF	[31]
ECs	ECs通过Norrin/Fzd4信号通路调控脑膜巨噬细胞的功能，发挥抗肿瘤作用。	CXCL4	[32]

TME细胞	作用	治疗靶点	参考文献
TILs	CD8⁺ CTL通过抗原特异性识别直接介导肿瘤细胞杀伤；CD4⁺ Th通过分泌细胞因子促进适应性免疫反应；Tregs抑制抗肿瘤免疫反应，促进肿瘤进展。	GZMA	[33,34]
	Tregs通过释放抗炎细胞因子来控制免疫细胞的活性。		[36,37]
TAMs	M2型TAMs由IL-4诱导释放生长因子，参与肿瘤进展和免疫抑制。	SPP1、CEBPB、OLFML2B、CD1C、NAT1	[42,43]
	TAMs浸润水平较低与复发率和远处转移风险的下降相关。		[52]
	M1型TAMs预示着更好的无进展生存期。		[3,37,53]
TAAs	TAAs通过分泌细胞因子、生长因子及上调肿瘤细胞生存基因的表达，促进脑肿瘤生长和进展。	HMGB1、PTPRZ1	[56,59]
	TAAs通过提供SHH配体激活Ptch1介导的非经典的SHH通路，诱导肿瘤细胞Nestin表达并解除Gli3对经典SHH信号通路的抑制，从而驱动肿瘤的起始与维持。		[56,60,61]
	坏死性TAAs分泌CCL2，激活JAK2/STAT3-Notch通路，维持转移性MB干细胞特性并驱动肿瘤进展。		[66]
	在复发性SHH-MB中，肿瘤细胞可以在BMPs刺激下转分化为TAAs，促进肿瘤进展。		[66,67]
TAFs	PDGF配体趋化性招募TAFs，并将其重编程为转移相关TAFs，通过分泌BMP等因子，增强MB在软脑膜的定植能力和转移灶生长。	PDGF	[31]
ECs	ECs通过Norrin/Fzd4信号通路调控脑膜巨噬细胞的功能，发挥抗肿瘤作用。	CXCL4	[32]

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