Advertisement
ResearchIn-Press PreviewCell biologyOncology Open Access | 10.1172/JCI173789
1Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, United States of America
2Department of Medicine, Division of Regenerative Medicine, Sanford Stem Cell Institute, UCSD, La Jolla, United States of America
3Department of Neurology, Northwestern University, Chicago, United States of America
4Department of Neurology, Northwestern University Feinberg School of Medicine, United States of America
5Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America
6Comprehensive Cancer Center, University of Chicago, Chicago, United States of America
7Biological Sciences Division, University of Chicago, Chicago, United States of America
8Department of Neurosurgery, University of Minnesota, Minneapolis, United States of America
9Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, United States of America
10Departments of Pathology and Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, United States of America
Find articles by Song, X. in: JCI | PubMed | Google Scholar
1Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, United States of America
2Department of Medicine, Division of Regenerative Medicine, Sanford Stem Cell Institute, UCSD, La Jolla, United States of America
3Department of Neurology, Northwestern University, Chicago, United States of America
4Department of Neurology, Northwestern University Feinberg School of Medicine, United States of America
5Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America
6Comprehensive Cancer Center, University of Chicago, Chicago, United States of America
7Biological Sciences Division, University of Chicago, Chicago, United States of America
8Department of Neurosurgery, University of Minnesota, Minneapolis, United States of America
9Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, United States of America
10Departments of Pathology and Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, United States of America
Find articles by Tiek, D. in: JCI | PubMed | Google Scholar |
1Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, United States of America
2Department of Medicine, Division of Regenerative Medicine, Sanford Stem Cell Institute, UCSD, La Jolla, United States of America
3Department of Neurology, Northwestern University, Chicago, United States of America
4Department of Neurology, Northwestern University Feinberg School of Medicine, United States of America
5Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America
6Comprehensive Cancer Center, University of Chicago, Chicago, United States of America
7Biological Sciences Division, University of Chicago, Chicago, United States of America
8Department of Neurosurgery, University of Minnesota, Minneapolis, United States of America
9Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, United States of America
10Departments of Pathology and Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, United States of America
Find articles by Miki, S. in: JCI | PubMed | Google Scholar
1Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, United States of America
2Department of Medicine, Division of Regenerative Medicine, Sanford Stem Cell Institute, UCSD, La Jolla, United States of America
3Department of Neurology, Northwestern University, Chicago, United States of America
4Department of Neurology, Northwestern University Feinberg School of Medicine, United States of America
5Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America
6Comprehensive Cancer Center, University of Chicago, Chicago, United States of America
7Biological Sciences Division, University of Chicago, Chicago, United States of America
8Department of Neurosurgery, University of Minnesota, Minneapolis, United States of America
9Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, United States of America
10Departments of Pathology and Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, United States of America
Find articles by Huang, T. in: JCI | PubMed | Google Scholar
1Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, United States of America
2Department of Medicine, Division of Regenerative Medicine, Sanford Stem Cell Institute, UCSD, La Jolla, United States of America
3Department of Neurology, Northwestern University, Chicago, United States of America
4Department of Neurology, Northwestern University Feinberg School of Medicine, United States of America
5Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America
6Comprehensive Cancer Center, University of Chicago, Chicago, United States of America
7Biological Sciences Division, University of Chicago, Chicago, United States of America
8Department of Neurosurgery, University of Minnesota, Minneapolis, United States of America
9Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, United States of America
10Departments of Pathology and Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, United States of America
Find articles by Lu, M. in: JCI | PubMed | Google Scholar
1Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, United States of America
2Department of Medicine, Division of Regenerative Medicine, Sanford Stem Cell Institute, UCSD, La Jolla, United States of America
3Department of Neurology, Northwestern University, Chicago, United States of America
4Department of Neurology, Northwestern University Feinberg School of Medicine, United States of America
5Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America
6Comprehensive Cancer Center, University of Chicago, Chicago, United States of America
7Biological Sciences Division, University of Chicago, Chicago, United States of America
8Department of Neurosurgery, University of Minnesota, Minneapolis, United States of America
9Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, United States of America
10Departments of Pathology and Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, United States of America
Find articles by Goenka, A. in: JCI | PubMed | Google Scholar
1Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, United States of America
2Department of Medicine, Division of Regenerative Medicine, Sanford Stem Cell Institute, UCSD, La Jolla, United States of America
3Department of Neurology, Northwestern University, Chicago, United States of America
4Department of Neurology, Northwestern University Feinberg School of Medicine, United States of America
5Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America
6Comprehensive Cancer Center, University of Chicago, Chicago, United States of America
7Biological Sciences Division, University of Chicago, Chicago, United States of America
8Department of Neurosurgery, University of Minnesota, Minneapolis, United States of America
9Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, United States of America
10Departments of Pathology and Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, United States of America
Find articles by Iglesia, R. in: JCI | PubMed | Google Scholar |
1Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, United States of America
2Department of Medicine, Division of Regenerative Medicine, Sanford Stem Cell Institute, UCSD, La Jolla, United States of America
3Department of Neurology, Northwestern University, Chicago, United States of America
4Department of Neurology, Northwestern University Feinberg School of Medicine, United States of America
5Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America
6Comprehensive Cancer Center, University of Chicago, Chicago, United States of America
7Biological Sciences Division, University of Chicago, Chicago, United States of America
8Department of Neurosurgery, University of Minnesota, Minneapolis, United States of America
9Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, United States of America
10Departments of Pathology and Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, United States of America
Find articles by Yu, X. in: JCI | PubMed | Google Scholar
1Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, United States of America
2Department of Medicine, Division of Regenerative Medicine, Sanford Stem Cell Institute, UCSD, La Jolla, United States of America
3Department of Neurology, Northwestern University, Chicago, United States of America
4Department of Neurology, Northwestern University Feinberg School of Medicine, United States of America
5Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America
6Comprehensive Cancer Center, University of Chicago, Chicago, United States of America
7Biological Sciences Division, University of Chicago, Chicago, United States of America
8Department of Neurosurgery, University of Minnesota, Minneapolis, United States of America
9Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, United States of America
10Departments of Pathology and Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, United States of America
Find articles by Wu, R. in: JCI | PubMed | Google Scholar
1Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, United States of America
2Department of Medicine, Division of Regenerative Medicine, Sanford Stem Cell Institute, UCSD, La Jolla, United States of America
3Department of Neurology, Northwestern University, Chicago, United States of America
4Department of Neurology, Northwestern University Feinberg School of Medicine, United States of America
5Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America
6Comprehensive Cancer Center, University of Chicago, Chicago, United States of America
7Biological Sciences Division, University of Chicago, Chicago, United States of America
8Department of Neurosurgery, University of Minnesota, Minneapolis, United States of America
9Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, United States of America
10Departments of Pathology and Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, United States of America
Find articles by Walker, M. in: JCI | PubMed | Google Scholar
1Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, United States of America
2Department of Medicine, Division of Regenerative Medicine, Sanford Stem Cell Institute, UCSD, La Jolla, United States of America
3Department of Neurology, Northwestern University, Chicago, United States of America
4Department of Neurology, Northwestern University Feinberg School of Medicine, United States of America
5Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America
6Comprehensive Cancer Center, University of Chicago, Chicago, United States of America
7Biological Sciences Division, University of Chicago, Chicago, United States of America
8Department of Neurosurgery, University of Minnesota, Minneapolis, United States of America
9Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, United States of America
10Departments of Pathology and Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, United States of America
Find articles by Zeng, C. in: JCI | PubMed | Google Scholar
1Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, United States of America
2Department of Medicine, Division of Regenerative Medicine, Sanford Stem Cell Institute, UCSD, La Jolla, United States of America
3Department of Neurology, Northwestern University, Chicago, United States of America
4Department of Neurology, Northwestern University Feinberg School of Medicine, United States of America
5Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America
6Comprehensive Cancer Center, University of Chicago, Chicago, United States of America
7Biological Sciences Division, University of Chicago, Chicago, United States of America
8Department of Neurosurgery, University of Minnesota, Minneapolis, United States of America
9Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, United States of America
10Departments of Pathology and Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, United States of America
Find articles by Shah, H. in: JCI | PubMed | Google Scholar |
1Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, United States of America
2Department of Medicine, Division of Regenerative Medicine, Sanford Stem Cell Institute, UCSD, La Jolla, United States of America
3Department of Neurology, Northwestern University, Chicago, United States of America
4Department of Neurology, Northwestern University Feinberg School of Medicine, United States of America
5Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America
6Comprehensive Cancer Center, University of Chicago, Chicago, United States of America
7Biological Sciences Division, University of Chicago, Chicago, United States of America
8Department of Neurosurgery, University of Minnesota, Minneapolis, United States of America
9Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, United States of America
10Departments of Pathology and Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, United States of America
Find articles by Weng, S. in: JCI | PubMed | Google Scholar
1Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, United States of America
2Department of Medicine, Division of Regenerative Medicine, Sanford Stem Cell Institute, UCSD, La Jolla, United States of America
3Department of Neurology, Northwestern University, Chicago, United States of America
4Department of Neurology, Northwestern University Feinberg School of Medicine, United States of America
5Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America
6Comprehensive Cancer Center, University of Chicago, Chicago, United States of America
7Biological Sciences Division, University of Chicago, Chicago, United States of America
8Department of Neurosurgery, University of Minnesota, Minneapolis, United States of America
9Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, United States of America
10Departments of Pathology and Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, United States of America
Find articles by Huff, A. in: JCI | PubMed | Google Scholar
1Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, United States of America
2Department of Medicine, Division of Regenerative Medicine, Sanford Stem Cell Institute, UCSD, La Jolla, United States of America
3Department of Neurology, Northwestern University, Chicago, United States of America
4Department of Neurology, Northwestern University Feinberg School of Medicine, United States of America
5Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America
6Comprehensive Cancer Center, University of Chicago, Chicago, United States of America
7Biological Sciences Division, University of Chicago, Chicago, United States of America
8Department of Neurosurgery, University of Minnesota, Minneapolis, United States of America
9Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, United States of America
10Departments of Pathology and Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, United States of America
Find articles by Zhang, W. in: JCI | PubMed | Google Scholar |
1Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, United States of America
2Department of Medicine, Division of Regenerative Medicine, Sanford Stem Cell Institute, UCSD, La Jolla, United States of America
3Department of Neurology, Northwestern University, Chicago, United States of America
4Department of Neurology, Northwestern University Feinberg School of Medicine, United States of America
5Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America
6Comprehensive Cancer Center, University of Chicago, Chicago, United States of America
7Biological Sciences Division, University of Chicago, Chicago, United States of America
8Department of Neurosurgery, University of Minnesota, Minneapolis, United States of America
9Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, United States of America
10Departments of Pathology and Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, United States of America
Find articles by Koga, T. in: JCI | PubMed | Google Scholar
1Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, United States of America
2Department of Medicine, Division of Regenerative Medicine, Sanford Stem Cell Institute, UCSD, La Jolla, United States of America
3Department of Neurology, Northwestern University, Chicago, United States of America
4Department of Neurology, Northwestern University Feinberg School of Medicine, United States of America
5Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America
6Comprehensive Cancer Center, University of Chicago, Chicago, United States of America
7Biological Sciences Division, University of Chicago, Chicago, United States of America
8Department of Neurosurgery, University of Minnesota, Minneapolis, United States of America
9Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, United States of America
10Departments of Pathology and Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, United States of America
Find articles by Hubert, C. in: JCI | PubMed | Google Scholar
1Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, United States of America
2Department of Medicine, Division of Regenerative Medicine, Sanford Stem Cell Institute, UCSD, La Jolla, United States of America
3Department of Neurology, Northwestern University, Chicago, United States of America
4Department of Neurology, Northwestern University Feinberg School of Medicine, United States of America
5Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America
6Comprehensive Cancer Center, University of Chicago, Chicago, United States of America
7Biological Sciences Division, University of Chicago, Chicago, United States of America
8Department of Neurosurgery, University of Minnesota, Minneapolis, United States of America
9Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, United States of America
10Departments of Pathology and Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, United States of America
Find articles by Horbinski, C. in: JCI | PubMed | Google Scholar |
1Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, United States of America
2Department of Medicine, Division of Regenerative Medicine, Sanford Stem Cell Institute, UCSD, La Jolla, United States of America
3Department of Neurology, Northwestern University, Chicago, United States of America
4Department of Neurology, Northwestern University Feinberg School of Medicine, United States of America
5Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America
6Comprehensive Cancer Center, University of Chicago, Chicago, United States of America
7Biological Sciences Division, University of Chicago, Chicago, United States of America
8Department of Neurosurgery, University of Minnesota, Minneapolis, United States of America
9Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, United States of America
10Departments of Pathology and Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, United States of America
Find articles by Furnari, F. in: JCI | PubMed | Google Scholar
1Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, United States of America
2Department of Medicine, Division of Regenerative Medicine, Sanford Stem Cell Institute, UCSD, La Jolla, United States of America
3Department of Neurology, Northwestern University, Chicago, United States of America
4Department of Neurology, Northwestern University Feinberg School of Medicine, United States of America
5Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America
6Comprehensive Cancer Center, University of Chicago, Chicago, United States of America
7Biological Sciences Division, University of Chicago, Chicago, United States of America
8Department of Neurosurgery, University of Minnesota, Minneapolis, United States of America
9Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, United States of America
10Departments of Pathology and Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, United States of America
Find articles by Hu, B. in: JCI | PubMed | Google Scholar
1Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, United States of America
2Department of Medicine, Division of Regenerative Medicine, Sanford Stem Cell Institute, UCSD, La Jolla, United States of America
3Department of Neurology, Northwestern University, Chicago, United States of America
4Department of Neurology, Northwestern University Feinberg School of Medicine, United States of America
5Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America
6Comprehensive Cancer Center, University of Chicago, Chicago, United States of America
7Biological Sciences Division, University of Chicago, Chicago, United States of America
8Department of Neurosurgery, University of Minnesota, Minneapolis, United States of America
9Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, United States of America
10Departments of Pathology and Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, United States of America
Find articles by Cheng, S. in: JCI | PubMed | Google Scholar
Published April 25, 2024 - More info
Widespread alterations in RNA alternative splicing (AS) have been identified in adult gliomas. However, their regulatory mechanism, biological significance, and therapeutic potential remain largely elusive. Here, using a computational approach with both bulk and single cell RNA-sequencing, we uncover a prognostic AS signature linked with neural developmental hierarchies. Using advanced iPSC glioma models driven by glioma driver mutations, we show that this AS signature could be enhanced by EGFRvIII and inhibited by in situ IDH1 mutation. Functional validation of two isoform switching events in CERS5 and MPZL1 shows regulations of sphingolipid metabolism and SHP2 signaling, respectively. Analysis of upstream RNA binding proteins reveals PTBP1 as a key regulator of the AS signature where targeting of PTBP1 suppresses tumor growth and promotes the expression of a neuron marker TUJ1 in glioma stem-like cells. Overall, our data highlights the role of AS in impacting glioma malignance and heterogeneity and its potential as a therapeutic vulnerability for treating adult gliomas.