Back

Chi3l1 is a modulator of glioma stem cell states and a therapeutic vulnerability for glioblastoma

Guetta-Terrier, C.; Karambizi, D.; Akosman, B.; Chen, J.-S.; Kamle, S.; Fajardo, J. E.; Fiser, A.; Singh, R.; Toms, S. A.; Lee, C. G.; Elias, J. A.; Tapinos, N.

2021-10-01 cancer biology
10.1101/2021.10.01.462786 bioRxiv
Show abstract

Chi3l1 (Chitinase 3-like 1) is a secreted protein highly expressed in glioblastoma. Here, we show that exposure of glioma stem cells (GSCs) to Chi3l1 reduces the CD133+/SOX2+ cells and increases the CD44+/Chi3l1+ cells. Chi3l1 binds to CD44 and induces phosphorylation and nuclear translocation of beta-catenin, Akt and STAT3. Single cell RNA-seq and RNA velocity following incubation of GSCs with Chi3l1 show significant changes in GSC state dynamics driving GSCs towards a mesenchymal expression profile and reducing transition probabilities towards terminal cellular states. ATAC-seq reveals that Chi3l1 increases accessibility of promoters containing MAZ transcription factor footprint. Inhibition of MAZ directly regulates genes with highest expression in cellular clusters exhibiting significant cell state transitions. Finally, targeting Chi3l1 in vivo with a blocking antibody, resets the transcriptomic profile of glioblastoma and inhibits tumor growth. Our work implicates Chi3l1 as modulator of GSC cellular states and demonstrates pre-clinical efficacy of anti-Chi3l1 antibody treatment.

Matching journals

The top 12 journals account for 50% of the predicted probability mass.

1
Cell Reports
○ 1498 papers in training set
Top 1%
11.8%
Similar papers in this journal
2
Nature Communications
○ 5641 papers in training set
Top 18%
9.7%
Similar papers in this journal
3
Cancer Research
● 130 papers in training set
Top 0.6%
5.5%
Similar papers in this journal
4
Proceedings of the National Academy of Sciences
● 2444 papers in training set
Top 12%
4.3%
Similar papers in this journal
5
Science Advances
● 1243 papers in training set
Top 8%
4.0%
Similar papers in this journal
6
iScience
○ 1154 papers in training set
Top 5%
4.0%
7
eLife
● 5828 papers in training set
Top 40%
2.6%
8
Cell Reports Medicine
○ 153 papers in training set
Top 2%
2.1%
9
NAR Cancer
◐ 37 papers in training set
Top 0.2%
2.0%
10
Cell Death & Disease
147 papers in training set
Top 2%
1.9%
11
Cell Stem Cell
○ 62 papers in training set
Top 0.8%
1.9%
12
Cancer Cell
○ 42 papers in training set
Top 0.7%
1.7%
50% of probability mass above
13
Communications Biology
○ 993 papers in training set
Top 14%
1.7%
14
Cancer Discovery
● 66 papers in training set
Top 1%
1.7%
15
PNAS Nexus
◐ 159 papers in training set
Top 1%
1.7%
16
Molecular Cancer Research
● 49 papers in training set
Top 0.7%
1.7%
17
Scientific Reports
○ 3612 papers in training set
Top 54%
1.7%
18
Molecular Cancer
○ 16 papers in training set
Top 0.1%
1.7%
19
Genome Medicine
○ 183 papers in training set
Top 3%
1.5%
20
Neuro-Oncology
◐ 36 papers in training set
Top 0.4%
1.3%
21
EMBO Molecular Medicine
○ 95 papers in training set
Top 1%
1.3%
22
PLOS Genetics
● 862 papers in training set
Top 9%
1.1%
23
Acta Neuropathologica Communications
○ 89 papers in training set
Top 2%
1.1%
24
BMC Biology
○ 265 papers in training set
Top 4%
1.0%
25
npj Precision Oncology
○ 53 papers in training set
Top 2%
1.0%
26
Clinical Cancer Research
● 64 papers in training set
Top 2%
0.9%
27
The EMBO Journal
○ 309 papers in training set
Top 6%
0.9%
28
Life Science Alliance
● 285 papers in training set
Top 7%
0.9%
29
Molecular Cell
○ 350 papers in training set
Top 5%
0.8%
30
Cancer Letters
○ 35 papers in training set
Top 1%
0.8%

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.