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Unravel cellular heterogeneity in IDH1-mutant low-grade glioma cell Lines

ABSTRACT: IDH1-mutant low-grade glioma are slow growing brain tumours arising from glial cells. They are subdivided in two groups; oligodendrogliomas and astrocytomas. They are characterizing by an intra-tumoral cellular heterogeneity. Previous studies have shown that at least 3 populations can be found in these tumours; astrocyte-like cells, oligodendrocyte-like cells and stem-like cells. Among these populations, some cells seem to be in a quiescent-like state, where others are mitotic. However, the correlation between glioma cell phenotype and cell cycle is still not fully explored. Here, using a low-grade glioma cell line named LGG275 published in Cancers 2021, 13(9), 2107; https://doi.org/10.3390/cancers13092107, we provided a method to sort at least two populations; the astrocyte-like cells and the oligodendrocyte-like cells, based on two extracellular markers, in a patient derived astrocytoma cell line. Proteomic analysis of these two populations as revealed that one is associated to a quiescent state, is plastic and can drive cellular heterogeneity, where the other is associated to an active state, and has a role in stem cell maintenance.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain, Neural Cell

DISEASE(S): Brain Glioma

SUBMITTER: Functional Proteomics Platform FPP

LAB HEAD: Jean-Philippe Hugnot

PROVIDER: PXD064235 | Pride | 2026-07-22

REPOSITORIES: Pride

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Source:

			Action	DRS
	RefProt_HUMAN_2025_01_FPPCON_v1.8.predicted.speclib	Other
	RefProteome_HUMAN-cano_2025_01_UP000005640_9606.fasta	Fasta
	TRI275_240326_EX_DIA2_CD44M_1_3_49.raw	Raw
	TRI275_240326_EX_DIA2_CD44M_2_3_49.raw	Raw
	TRI275_240326_EX_DIA2_CD44M_3_2_49.raw	Raw

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Project description:One way by which astrocytes modulate oligodendrocytes’ activity is by delivering neurotransmitters and leukemia inhibitory factor (Lif) in the medium that bind oligodendrocyte receptors. Most of these receptors are involved in intercellular Ca2+-signaling (ICS). However, not much is known about the interactions between myelination (MYE) and ICS genes and how astrocyte nearness modulates the oligodendrocyte genomic myelination fabric. We profiled the transcriptomes of immortalized oligodendrocyte precursor cells (Oli-neu) when cultured alone or co-cultured with cortical astrocytes. The astrocytes were plated in cell culture insert systems that did not allow formation of gap junction channels with oligodendrocytes but permitted exchange of soluble factors via the culture medium. Remarkably, astrocyte proximity induced a larger increase of the overall expression level and interlinkage of MYE genes than the differentiating 10d treatment with 1 mM dibutyryl cAMP that turns Oli-neu cells into myelin-associated glycoprotein-positive oligodendrocyte-like cells. Moreover, more MYE and ICS genes were turned on and fewer turned off by astrocyte proximity than by differentiating treatment. Lif receptor was up-regulated by astrocyte proximity but not by the differentiating treatment. We have identified the responsible transcriptomic networks by which the intercellular ICS gene web controls MYE gene web, with genes encoding the gap junction proteins (connexins, Cx) Cx29, Cx32 and Cx47 playing central roles. The novel Prominent Gene Analysis (that refines iteratively the functional webs to optimize the interconnectivity and expression stability of the associated genes) was used to select and rank the most relevant MYE and ICS genes and build the corresponding gene webs. Determine the modifications of the myelination transcriptome induced in Oli- neu control cells by differentiating treatment and proximity of cortical astrocytes. Four culture dishes of each of control, differentiated and in the astrocyte proximity Oli-neu cells were profiled using Duke mouse 30K and 36k oligonucleotide arrays in the "multiple yellow" hybrization design.

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Unravel cellular heterogeneity in IDH1-mutant low-grade glioma cell Lines

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