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Combined targeting of glioblastoma stem cells of different cellular states disrupts malignant progression

The molecular mechanisms underlying the function of different cellular states in glioblastoma stem cells (GSCs) remain poorly understood. Here, the authors perform integrated single cell and bulk analysis of GSCs and identify potential therapeutic targets.

Chenfei Lu
Tao Kang
Xiuxing Wang
ResearchOpen Access26 Mar 2025
Nature Communications

Volume: 16, P: 1-21
Lymphatic endothelial-like cells promote glioblastoma stem cell growth through cytokine-driven cholesterol metabolism

Rich and colleagues identify that lymphatic endothelial-like cells in glioblastoma drive the growth of cancer stem cells via CCL21–CCR7 signaling, inducing KAT5 to acetylate HMGSC1, which enhances its protein stability and cholesterol synthesis.

Linjie Zhao
Zhixin Qiu
Jeremy N. Rich
Research03 Jan 2024
Nature Cancer

Volume: 5, P: 147-166
LncRNA INHEG promotes glioma stem cell maintenance and tumorigenicity through regulating rRNA 2’-O-methylation

Long noncoding RNAs (lncRNAs) may contribute to cancer progression. Here the authors show that LncRNA INHEG modulates rRNA 2’-O-methylation and facilitates mRNA translation to promote glioma stem cell renewal and growth.

Lihui Liu
Ziyang Liu
Runsheng Chen
ResearchOpen Access18 Nov 2023
Nature Communications

Volume: 14, P: 1-18
Targeting glioma stem cells through combined BMI1 and EZH2 inhibition

Microenvironmental pressures in glioblastoma select for glioma stem cells (GSCs) subpopulations that are maintained through preferential activation of BMI1 and EZH2 in different niches. Given the high degree of intratumor heterogeneity, combined pharmacological inhibition of Polycomb repressive complexes targets proneural and mesenchynmal GSCs and expands lifespan in mice, warranting the therapeutic evaluation of this approach in patients with glioblastoma.

Xun Jin
Leo J Y Kim
Jeremy N Rich
Research09 Oct 2017
Nature Medicine

Volume: 23, P: 1352-1361
Three-dimensional bioprinted glioblastoma microenvironments model cellular dependencies and immune interactions

Min Tang
Qi Xie
Jeremy N. Rich
Research04 Jun 2020
Cell Research

Volume: 30, P: 833-853
Therapeutic targeting of ependymoma as informed by oncogenic enhancer profiling

Super enhancers regulate oncogenes and other molecular targets in ependymomas, and identification of these genes provides potential therapeutic targets.

Stephen C. Mack
Kristian W. Pajtler
Jeremy N. Rich
Research20 Dec 2017
Nature

Volume: 553, P: 101-105
IFI35 regulates non-canonical NF-κB signaling to maintain glioblastoma stem cells and recruit tumor-associated macrophages

Daqi Li
Xiefeng Wang
Xiuxing Wang
Research09 Apr 2024
Cell Death & Differentiation

Volume: 31, P: 738-752
Brain cancer stem cells: resilience through adaptive plasticity and hierarchical heterogeneity

This Review discusses molecular circuitry underlying adaptive plasticity in brain cancer stem cells, highlighting the transcriptional classification of the stem cell state, neoplastic evolution and development of therapeutic resilience, and critical brain-specific microenvironmental inputs with the goal of informing next-generation stem-targeted treatment paradigms.

Ryan C. Gimple
Kailin Yang
Jeremy N. Rich
Reviews16 Jun 2022
Nature Reviews Cancer

Volume: 22, P: 497-514

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