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单细胞空间生物学可解析儿童脑病理学的发育时间过程。

Single cell spatial biology over developmental time can decipher pediatric brain pathologies.

机构信息

Computational Structural Biology Section, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA; Cancer Innovation Laboratory, National Cancer Institute at Frederick, Frederick, MD 21702, USA; Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.

Cancer Innovation Laboratory, National Cancer Institute at Frederick, Frederick, MD 21702, USA.

出版信息

Neurobiol Dis. 2024 Sep;199:106597. doi: 10.1016/j.nbd.2024.106597. Epub 2024 Jul 9.


DOI:10.1016/j.nbd.2024.106597
PMID:38992777
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11286356/
Abstract

Pediatric low grade brain tumors and neurodevelopmental disorders share proteins, signaling pathways, and networks. They also share germline mutations and an impaired prenatal differentiation origin. They may differ in the timing of the events and proliferation. We suggest that their pivotal distinct, albeit partially overlapping, outcomes relate to the cell states, which depend on their spatial location, and timing of gene expression during brain development. These attributes are crucial as the brain develops sequentially, and single-cell spatial organization influences cell state, thus function. Our underlying premise is that the root cause in neurodevelopmental disorders and pediatric tumors is impaired prenatal differentiation. Data related to pediatric brain tumors, neurodevelopmental disorders, brain cell (sub)types, locations, and timing of expression in the developing brain are scant. However, emerging single cell technologies, including transcriptomic, spatial biology, spatial high-resolution imaging performed over the brain developmental time, could be transformational in deciphering brain pathologies thereby pharmacology.

摘要

儿科低度脑肿瘤和神经发育障碍共享蛋白质、信号通路和网络。它们还共享种系突变和受损的产前分化起源。它们在事件和增殖的时间上可能不同。我们认为,它们关键的不同,尽管部分重叠,但其结果与细胞状态有关,细胞状态取决于大脑发育过程中的空间位置和基因表达的时间。这些属性是至关重要的,因为大脑是按顺序发育的,单细胞的空间组织会影响细胞状态,从而影响功能。我们的基本前提是,神经发育障碍和儿科肿瘤的根本原因是产前分化受损。与儿科脑肿瘤、神经发育障碍、脑细胞(亚)类型、发育中大脑的位置和表达时间相关的数据很少。然而,新兴的单细胞技术,包括转录组学、空间生物学、在大脑发育时间内进行的空间高分辨率成像,可以改变对大脑病理学的理解,从而改变药理学。

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本文引用的文献

[1]
Mitogen signaling strength and duration can control cell cycle decisions.

Sci Adv. 2024-7-5

[2]
Spatial and temporal pattern of structure-function coupling of human brain connectome with development.

Elife. 2024-6-20

[3]
Modeling gene expression cascades during cell state transitions.

iScience. 2024-3-4

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Pediatric low-grade glioma models: advances and ongoing challenges.

Front Oncol. 2024-1-22

[5]
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Front Cell Neurosci. 2023-11-28

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Cell Mol Life Sci. 2023-12-12

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Trends Genet. 2024-2

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Cancer and Autism: How PTEN Mutations Degrade Function at the Membrane and Isoform Expression in the Human Brain.

J Mol Biol. 2023-12-15

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Neurodevelopmental disorders and cancer networks share pathways, but differ in mechanisms, signaling strength, and outcome.

NPJ Genom Med. 2023-11-4

[10]
Protein conformational ensembles in function: roles and mechanisms.

RSC Chem Biol. 2023-9-5

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