scholarly journals Quiescent stem cell marker genes in glioma gene networks are sufficient to distinguish between normal and glioblastoma (GBM) samples. 

2020 ◽  
Author(s):  
Shradha Mukherjee

Abstract Grade 4 glioma or GBM has poor prognosis and is the most aggressive grade of glioma. Accurate diagnosis and classification of tumor grade is a critical determinant for development of treatment pathway. Extensive genomic sequencing of gliomas, different cell types, brain tissue regions and advances in bioinformatics algorithms, have presented an opportunity to identify molecular markers that can complement existing histology and imaging methods used to diagnose and classify gliomas. ‘Cancer stem cell theory’ purports that a minor population of stem cells among the heterogeneous population of different cell types in the tumor, drive tumor growth and resistance to therapies. However, characterization of stem cell states in GBM and ability of stem cell state signature genes to serve as diagnostic or prognostic molecular markers are unknown. In this work, two different network construction algorithms, Weighted correlation network analysis (WGCNA) and Multiscale Clustering of Geometric Network (MEGENA), were applied on publicly available glioma, control brain and stem cell gene expression RNA-seq datasets, to identify gene network regulatory modules associated with GBM. Both gene network algorithms identified consensus or equivalent modules, HuAgeGBsplit_18 (WGCNA) and c1_HuAgeGBsplit_32/193 (MEGENA), significantly associated with GBM. Characterization of HuAgeGBsplit_18 (WGCNA) and c1_HuAgeGBsplit_32/193 (MEGENA) modules showed significant enrichment of rodent quiescent stem cell marker genes (GSE70696_QNPbyTAP). A logistic regression model built with eight of these quiescent stem cell marker genes (GSE70696_QNPbyTAP) was sufficient to distinguish between control and GBM samples. This study demonstrates that GBM associated gene regulatory modules are characterized by diagnostic quiescent stem cell marker genes, which may potentially be used clinically as diagnostic markers and therapeutic targets in GBM.

2021 ◽  
Vol 53 (1) ◽  
pp. 1-7
Author(s):  
Jinyoung Lee ◽  
Yongcheol Cho

AbstractAxon regeneration is orchestrated by many genes that are differentially expressed in response to injury. Through a comparative analysis of gene expression profiling, injury-responsive genes that are potential targets for understanding the mechanisms underlying regeneration have been revealed. As the efficiency of axon regeneration in both the peripheral and central nervous systems can be manipulated, we suggest that identifying regeneration-associated genes is a promising approach for developing therapeutic applications in vivo. Here, we review the possible roles of stem cell marker- or stemness-related genes in axon regeneration to gain a better understanding of the regeneration mechanism and to identify targets that can enhance regenerative capacity.


2019 ◽  
Vol 9 (7) ◽  
pp. 904-913
Author(s):  
Bing Yan ◽  
Ruining Liang ◽  
Meng Ji ◽  
Qi-Qige Wuyun ◽  
Weijun Guan ◽  
...  

Of all the significant researches that have taken place in isolation, culture and characterization of mesenchymal stem cells (MSCs), the field of kidney-derived mesenchymal stem cells (KMSCs) in Tibetan mastiff is still a blank. Therefore, the purpose of this study is to isolate, culture and characterize the Tibetan mastiff KMSCs. The KMSCs were successfully isolated from one-day year old Tibetan mastiff kidney, cultured for 16 passages and distinguished by two methods: immunofluorescence staining and RT-PCR. The Tibetan mastiff KMSCs expressed specific surface marker genes (VIM, CD44, FN1, CD90, CD109, CD73, FN1) and kidney marker gene PAX2. The proliferation ability of Tibetan mastiff KMSCs was measured through cell count and clonality. Furthermore, cells differentiated into different cell types (hepatocellular cells, osteogenic cells, adipogenic cells and chondrogenic cells) under special induced medium, and the marker genes of induced cells were identified with Immunofluorescence staining and RT-PCR. All of these results indicated that the Tibetan mastiff KMSCs were obtained successfully, which possessed certain characteristics of multipotent stem cells. Therefore, MSCs in Tibetan mastiff kidney hold potential for clinical applications for regenerative therapy and their further studies are waiting to be required to investigate their functions.


Immunity ◽  
1999 ◽  
Vol 10 (6) ◽  
pp. 691-700 ◽  
Author(s):  
Oleksi Petrenko ◽  
Andrew Beavis ◽  
Michele Klaine ◽  
Raja Kittappa ◽  
Isabelle Godin ◽  
...  

2004 ◽  
Vol 316 (3) ◽  
pp. 369-376 ◽  
Author(s):  
Maria V. T. Lobo ◽  
Maria I. Arenas ◽  
F. Javier M. Alonso ◽  
Gonzalo Gomez ◽  
Eulalia Baz�n ◽  
...  

2021 ◽  
Author(s):  
Patrick A. Fletcher ◽  
Rafael M. Prévide ◽  
Kosara Smiljanic ◽  
Arthur Sherman ◽  
Steven L. Coon ◽  
...  

AbstractThe mammalian pituitary gland is a complex organ consisting of hormone-producing cells (HPC), nonhormonal folliculostellate cells (FSC) and pituicytes, vascular pericytes and endothelial cells, and putative Sox2-expressing stem cells. Here, we used scRNAseq analysis of adult female rat pituitary cells to study the heterogeneity of pituitary cells with a focus on evaluating the transcriptomic profile of the Sox2-expressing population. Samples containing whole pituitary and separated anterior and posterior lobe cells allowed the identification of all expected pituitary resident cell types and lobe-specific subpopulations of vascular cells. Sox2 was expressed uniformly in all FSC, pituicytes, and a fraction of HPC. FSC comprised two subclusters; FSC1 contained more cells but expressed less genetic diversity compared to FSC2. The latter contained proliferative cells, expressed genes consistent with stem cell niche formation, including tight junctions, and shared genes with HPC. The FSC2 transcriptome profile was also consistent with the activity of pathways regulating cell proliferation and stem cell pluripotency, including the Hippo and Wnt pathways. The expression of other stem cell marker genes was common for FSC and pituicytes (Sox9, Cd9, Hes1, Vim, S100b) or cell type-specific (FSC: Prop1, Prrx1, Pitx1, Pitx2, Lhx3; pituicytes: Fgf10, Tbx3, Lhx2, Nkx2-1, Rax). FSC and pituicytes also expressed other astroglial marker genes, some common and other distinct, consistent with their identities as astroglial cells of the pituitary. These data suggest functional heterogeneity of FSC, with a larger fraction representing classical FSC, and a smaller fraction containing active stem-like cells and HPC-committed progenitors.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii201-ii201
Author(s):  
Patricia Tiburcio ◽  
Mary Locke ◽  
Srivydia Bhaskara ◽  
Mahesh Chandrasekharan ◽  
Eric Huang

Abstract Heterozygous mutations in the isocitrate dehydrogenase 1 (IDH1) gene are most common in glioma, resulting in predominantly arginine to histidine substitution at codon 132. Because IDH1R132H requires a wild-type allele to produce (D)-2-hydroxyglutarate for epigenetic reprogramming, glioma cells with loss of the remaining wild-type allele (hence IDH1R132H-hemizygous) exhibit an IDH1-wild-type-like glioma phenotype and aggressive tumor growth. Although previous studies reported that transgenic IDH1R132H induced the expression of nestin—a glioma stem-cell marker, the underlying mechanism remains unclear. Furthermore, this finding seems at odds with the better outcome of IDH-mutant glioma owing to a negative association of nestin with overall survival. To gain a comprehensive understanding of glioma stem-cell marker gene regulation in IDH-mutant glioma, we compared gene expression between IDH1R132H-heterozygous and IDH1R132H-hemizygous glioma cells under adherent and spheroid growth conditions and found that glioma stem-cell marker genes, including CD44, NES, and PROM1, are generally downregulated in the spheroid growth of IDH1R132H-heterozygous cells. This result was validated in patient samples of IDH-mutant glioma compared with those of IDH-wildtype glioma, even though modest NES upregulation was observed in the adherent growth of IDH1R132H-hemizygous glioma cells. In contrast, CD24 is specifically upregulated in the spheroid growth of IDH1R132H-heterozygous cells and patient samples of IDH-mutant glioma and is apparently associated with better survival. Mechanistically, CD24 and NES expression responds differentially to alteration of (D)-2-hydroxyglutarate levels. CD24 upregulation is associated with histone and DNA demethylation as opposed to hypermethylation in those downregulated glioma stem-cell marker genes. Therefore, the better outcome of IDH-mutant glioma is orchestrated exquisitely through epigenetic reprogramming that directs bidirectional expression of glioma stem-cell marker genes.


Sign in / Sign up

Export Citation Format

Share Document