Inferred Developmental Origins of Brain Tumors from Single Cell RNA-Sequencing Data DOI Creative Commons
Su Wang, Rachel Naomi Curry, Malcolm F. McDonald

et al.

Neuro-Oncology Advances, Journal Year: 2025, Volume and Issue: 7(1)

Published: Jan. 1, 2025

Abstract Background The reactivation of neurodevelopmental programs in cancer highlights parallel biological processes that occur both normal development and brain tumors. Achieving a deeper understanding how dysregulated developmental factors play role the progression tumors is therefore crucial for identifying potential targets therapeutic interventions. Single-cell RNA-sequencing (scRNA-Seq) provides an opportunity to understand are reinitiated at single-cell resolution. aim this study identify origins using scRNA-Seq data. Methods Here, we introduce COORS (Cell Of ORigin like CellS), computational tool trained on human datasets annotates “developmental-like” cell states leverages type-specific multilayer perceptron models incorporates type tree reflects hierarchical relationships probabilities. Results Applying various datasets, including medulloblastoma (MB), glioma, diffuse midline glioma (DMG), identified developmental-like cells represent putative origin these Our method classification age regression, offering insights into types tumor subgroups. outer radial glia within IDHWT whereas oligodendrocyte precursor (OPCs) neuronal-like IDHMut. Interestingly, IDHMut subgroup map OPC show bimodal distributions early late weeks development. Furthermore, offers valuable resource by providing novel markers linked MB, DMG Conclusions work adds our cumulative heterogeneity helps pave way tailored treatment strategies.

Language: Английский

Human cerebral organoids — a new tool for clinical neurology research DOI Open Access
Oliver L. Eichmüller, Juergen A. Knoblich

Nature Reviews Neurology, Journal Year: 2022, Volume and Issue: 18(11), P. 661 - 680

Published: Oct. 17, 2022

Language: Английский

Citations

174

Cellular development and evolution of the mammalian cerebellum DOI Creative Commons
Mari Sepp, Kevin Leiss, Florent Murat

et al.

Nature, Journal Year: 2023, Volume and Issue: 625(7996), P. 788 - 796

Published: Nov. 29, 2023

The expansion of the neocortex, a hallmark mammalian evolution

Language: Английский

Citations

63

The single-cell and spatial transcriptional landscape of human gastrulation and early brain development DOI Creative Commons
Bo Zeng, Zeyuan Liu,

Yufeng Lu

et al.

Cell stem cell, Journal Year: 2023, Volume and Issue: 30(6), P. 851 - 866.e7

Published: May 15, 2023

The emergence of the three germ layers and lineage-specific precursor cells orchestrating organogenesis represent fundamental milestones during early embryonic development. We analyzed transcriptional profiles over 400,000 from 14 human samples collected post-conceptional weeks (PCW) 3 to 12 delineate dynamic molecular cellular landscape gastrulation nervous system described diversification cell types, spatial patterning neural tube cells, signaling pathways likely involved in transforming epiblast into neuroepithelial then radial glia. resolved 24 clusters glial along outlined differentiation trajectories for main classes neurons. Lastly, we identified conserved distinctive features across species by comparing single-cell transcriptomic between humans mice. This comprehensive atlas sheds light on mechanisms underlying brain

Language: Английский

Citations

57

Human cerebellar organoids with functional Purkinje cells DOI Creative Commons
Alexander Atamian, Marcella Birtele, Negar Hosseini

et al.

Cell stem cell, Journal Year: 2024, Volume and Issue: 31(1), P. 39 - 51.e6

Published: Jan. 1, 2024

Language: Английский

Citations

39

Converging mechanism of UM171 and KBTBD4 neomorphic cancer mutations DOI Creative Commons
Xiaowen Xie, Olivia Zhang, Megan J. R. Yeo

et al.

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 12, 2025

Language: Английский

Citations

9

Cancer-selective metabolic vulnerabilities in MYC-amplified medulloblastoma DOI Creative Commons
William D. Gwynne, Yujin Suk, Stefan Custers

et al.

Cancer Cell, Journal Year: 2022, Volume and Issue: 40(12), P. 1488 - 1502.e7

Published: Nov. 10, 2022

Language: Английский

Citations

47

Modeling epigenetic lesions that cause gliomas DOI
Gilbert J. Rahme, Nauman Javed,

Kaitlyn L. Puorro

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(17), P. 3674 - 3685.e14

Published: July 25, 2023

Language: Английский

Citations

38

Neuron–oligodendroglial interactions in health and malignant disease DOI
Kathryn R. Taylor, Michelle Monje

Nature reviews. Neuroscience, Journal Year: 2023, Volume and Issue: 24(12), P. 733 - 746

Published: Oct. 19, 2023

Language: Английский

Citations

33

Mapping pediatric brain tumors to their origins in the developing cerebellum DOI Creative Commons
Konstantin Okonechnikov, Piyush Joshi, Mari Sepp

et al.

Neuro-Oncology, Journal Year: 2023, Volume and Issue: 25(10), P. 1895 - 1909

Published: Aug. 3, 2023

Abstract Background Distinguishing the cellular origins of childhood brain tumors is key for understanding tumor initiation and identifying lineage-restricted, tumor-specific therapeutic targets. Previous strategies to map cell-of-origin typically involved comparing human murine embryonal tissues, which potentially limited due species-specific differences. The aim this study was unravel 3 most common pediatric tumors, ependymoma, pilocytic astrocytoma, medulloblastoma, using a developing cerebellar atlas. Methods We used single-nucleus atlas normal cerebellum consisting 176 645 cells as reference an in-depth comparison 4416 bulk single-cell transcriptome datasets, gene set variation analysis, correlation, matching techniques. Results find that astroglial lineage origin posterior fossa ependymomas. propose infratentorial astrocytomas originate from oligodendrocyte MHC II genes are specifically enriched in these tumors. confirm SHH Group 3/4 medulloblastomas granule cell unipolar brush lineages. Radiation-induced gliomas stem glial lineages demonstrate distinct primary medulloblastoma. identify expressed origin, specific; both sets represent promising targets future study. Conclusion Based on our results, individual within may resemble different types along restricted developmental lineage. Therefore, we suggest can arise multiple states “lineage origin.”

Language: Английский

Citations

23

Heterogeneity and tumoral origin of medulloblastoma in the single-cell era DOI Creative Commons

Hui Sheng,

Haotai Li,

Han Zeng

et al.

Oncogene, Journal Year: 2024, Volume and Issue: 43(12), P. 839 - 850

Published: Feb. 14, 2024

Abstract Medulloblastoma is one of the most common malignant pediatric brain tumors derived from posterior fossa. The current treatment includes maximal safe surgical resection, radiotherapy, whole cranio-spinal radiation and adjuvant with chemotherapy. However, it can only limitedly prolong survival time severe side effects relapse. Defining intratumoral heterogeneity, cellular origin identifying interaction network within tumor microenvironment are helpful for understanding mechanisms medulloblastoma tumorigenesis Due to technological limitations, heterogeneity have not been fully understood. Recently, emergence single-cell technology has provided a powerful tool achieving goal tumorigenesis. Several studies demonstrated each subtype utilizing RNA-seq, which uncovered before using conventional technologies. In this review, we present an overview progress in discuss novel findings age

Language: Английский

Citations

9