scholarly journals Childhood Cerebellar Tumors Mirror Conserved Fetal Transcriptional Programs

2018 ◽  
Author(s):  
Maria C Vladoiu ◽  
Ibrahim El-Hamamy ◽  
Laura K Donovan ◽  
Hamza Farooq ◽  
Borja L Holgado ◽  
...  
Keyword(s):  
Single Cell ◽  
Brush Cells ◽  
Group 4 ◽  
Divergent Differentiation ◽  
Unipolar Brush Cells ◽  
Early Brain Development ◽  
Group 3 ◽  
Cerebellar Tumours ◽  
Proximate Explanation ◽  
Cerebellar Cells

SummaryThe study of the origin and development of cerebellar tumours has been hampered by the complexity and heterogeneity of cerebellar cells that change over the course of development. We used single-cell transcriptomics to study >60,000 cells from the developing murine cerebellum, and show that different molecular subgroups of childhood cerebellar tumors mirror the transcription of cells from distinct, temporally restricted cerebellar lineages. Sonic Hedgehog medulloblastoma transcriptionally mirrors the granule cell hierarchy as expected, whereas Group 3 medulloblastoma resemble Nestin+ve stem cells, Group 4 medulloblastomas resemble unipolar brush cells, and PFA/PFB ependymoma and cerebellar pilocytic astrocytoma resemble the prenatal gliogenic progenitor cells. Furthermore, single-cell transcriptomics of human childhood cerebellar tumors demonstrates that many bulk tumors contain a mixed population of cells with divergent differentiation. Our data highlight cerebellar tumors as a disorder of early brain development, and provide a proximate explanation for the peak incidence of cerebellar tumors in early childhood.

EPCO-26. INTEGRATIVE MULTI-OMICS IDENTIFIES CONVERGING DEVELOPMENTAL ORIGINS OF DISTINCT MEDULLOBLASTOMA SUBGROUPS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi7-vi7
Author(s):  
Kyle Smith ◽  
Laure Bihannic ◽  
Brian Gudenas ◽  
Qingsong Gao ◽  
Parthiv Haldipur ◽  
...  
Keyword(s):  
Single Cell ◽  
Developmental Trajectories ◽  
Cell Lineage ◽  
Cell Types ◽  
Lineage Tracing ◽  
Group 4 ◽  
Group 3 ◽  
Mechanistic Basis ◽  
Rhombic Lip

Abstract Understanding the interplay between normal development and tumorigenesis, including the identification and characterization of lineage-specific origins of MB, is a fundamental challenge in the field. Recent studies have highlighted novel associations between biologically distinct MB subgroups and diverse murine cerebellar lineages via cross-species single-cell transcriptomics. Specifically, Group 4-MB correlated with the unipolar brush cell lineage and Group 3-MB resembled Nestin+ stem cells of the early cerebellum. However, these analyses were hampered by low resolution due to the sparsity of pertinent cerebellar cell types and the cross-species nature of the approach. Herein, we profoundly expand the depth of these rare developmental populations in the murine cerebellum using a combination of lineage tracing and integrative multi-omics. Isolation and enrichment of spatially and temporally unique developmental trajectories of key rhombic lip-derived glutamatergic lineages provided an enhanced reference for mapping MB subgroups based on molecular overlap, especially for poorly defined Group 3- and Group 4-MB. Further comparisons to a novel single-cell atlas of the human fetal cerebellum, companioned with laser-capture microdissected transcriptional and epigenetic datasets, reinforced developmental insights extracted from the mouse. Characterization of compartment-specific transcriptional programs and co-expression networks identified in the human upper rhombic lip implicated convergent cellular correlates of Group 3- and Group 4-MB, suggestive of a common developmental link. Together, our results strongly implicate developmental lineages of the upper rhombic lip as the probable origins of poorly defined Group 3- and Group 4-MB. These important findings will shape future efforts to accurately model the biological heterogeneity underlying these subgroups and provide unprecedented opportunities to explore their cellular and mechanistic basis.

scholarly journals PDTM-32. RESOLVING MEDULLOBLASTOMA CELLULAR ARCHITECTURE BY SINGLE-CELL GENOMICS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi194-vi194
Author(s):  
Laure Bihannic ◽  
Volker Hovestadt ◽  
Kyle Smith ◽  
Mariella Filbin ◽  
McKenzie Shaw ◽  
...  
Keyword(s):  
Single Cell ◽  
Developmental Trajectory ◽  
Cerebellar Tumor ◽  
Granule Neurons ◽  
Age Group ◽  
Molecular Subgroups ◽  
Developmental States ◽  
Group 4 ◽  
Cells Of Origin ◽  
Group 3

Abstract Medulloblastoma is a malignant childhood cerebellar tumor comprised of distinct molecular subgroups. Whereas genomic characteristics of these subgroups are well defined, the extent to which cellular diversity underlies their divergent biology and clinical behaviour remains largely unexplored. We used single-cell transcriptomics to investigate intra- and inter-tumoral heterogeneity in twenty-five medulloblastomas spanning all molecular subgroups. WNT, SHH, and Group 3 tumors comprised subgroup-specific undifferentiated and differentiated neuronal-like malignant populations, whereas Group 4 tumors were exclusively comprised of differentiated neuronal-like neoplastic cells. SHH tumors closely resembled granule neurons of varying differentiation states that correlated with patient age. Group 3 and Group 4 tumors exhibited a developmental trajectory from primitive progenitor-like to more mature neuronal-like cells, whose relative proportions distinguished these subgroups. Cross-species transcriptomics defined distinct glutamatergic populations as putative cells-of-origin for SHH and Group 4 subtypes. Collectively, these data provide novel insights into the cellular and developmental states underlying subtype-specific medulloblastoma biology.

scholarly journals Novel Molecular Hallmarks of Group 3 Medulloblastoma by Single-Cell Transcriptomics

2021 ◽  
Vol 11 ◽  
Author(s):  
Chaoying Qin ◽  
Yimin Pan ◽  
Yuzhe Li ◽  
Yue Li ◽  
Wenyong Long ◽  
...  
Keyword(s):  
Single Cell ◽  
Rna Sequencing ◽  
Pediatric Brain Tumors ◽  
Molecular Characteristics ◽  
Specific Cell ◽  
Cellular Mechanisms ◽  
Myc Oncogene ◽  
Molecular Features ◽  
Group 4 ◽  
Group 3

Medulloblastoma (MB) is a highly heterogeneous and one of the most malignant pediatric brain tumors, comprising four subgroups: Sonic Hedgehog, Wingless, Group 3, and Group 4. Group 3 MB has the worst prognosis of all MBs. However, the molecular and cellular mechanisms driving the maintenance of malignancy are poorly understood. Here, we employed high-throughput single-cell and bulk RNA sequencing to identify novel molecular features of Group 3 MB, and found that a specific cell cluster displayed a highly malignant phenotype. Then, we identified the glutamate receptor metabotropic 8 (GRM8), and AP-1 complex subunit sigma-2 (AP1S2) genes as two critical markers of Group 3 MB, corresponding to its poor prognosis. Information on 33 clinical cases was further utilized for validation. Meanwhile, a global map of the molecular cascade downstream of the MYC oncogene in Group 3 MB was also delineated using single-cell RNA sequencing. Our data yields new insights into Group 3 MB molecular characteristics and provides novel therapeutic targets for this relentless disease.

Morphological Changes in the Rat Granulosa Cell Surface During Differentiation Induced by Estradiol and Gonadotropins

1977 ◽  
Vol 35 ◽  
pp. 484-485
Author(s):  
P. Bagavandoss ◽  
JoAnne S. Richards ◽  
A. Rees Midgley
Keyword(s):  
Cell Surface ◽  
Granulosa Cell ◽  
Morphological Changes ◽  
Follicular Development ◽  
Female Rats ◽  
Functional Changes ◽  
Group 4 ◽  
Group 3 ◽  
Group 5 ◽  
Group 2

During follicular development in the mammalian ovary, several functional changes occur in the granulosa cells in response to steroid hormones and gonadotropins (1,2). In particular, marked changes in the content of membrane-associated receptors for the gonadotropins have been observed (1).We report here scanning electron microscope observations of morphological changes that occur on the granulosa cell surface in response to the administration of estradiol, human follicle stimulating hormone (hFSH), and human chorionic gonadotropin (hCG).Immature female rats that were hypophysectcmized on day 24 of age were treated in the following manner. Group 1: control groups were injected once a day with 0.1 ml phosphate buffered saline (PBS) for 3 days; group 2: estradiol (1.5 mg/0.2 ml propylene glycol) once a day for 3 days; group 3: estradiol for 3 days followed by 2 days of hFSH (1 μg/0.1 ml) twice daily, group 4: same as in group 3; group 5: same as in group 3 with a final injection of hCG (5 IU/0.1 ml) on the fifth day.

Correlation of γ-radioactivity and Scanning Electron Microscopy in measurement of retention of 111Indium-labeled canine endothelial cells on synthetic vascular grafts

1989 ◽  
Vol 47 ◽  
pp. 886-887
Author(s):  
E.J. Prendiville ◽  
S. Laliberté Verdon ◽  
K. E. Gould ◽  
K. Ramberg ◽  
R. J. Connolly ◽  
...  
Keyword(s):  
Blood Flow ◽  
Ex Vivo ◽  
Vascular Grafts ◽  
Retention Data ◽  
Vascular Prostheses ◽  
Group 4 ◽  
Human Fibronectin ◽  
Insufficient Time ◽  
Group 3 ◽  
Group 2

Endothelial cell (EC) seeding is postulated as a mechanism of improving patency in small caliber vascular grafts. However the majority of seeded EC are lost within 24 hours of restoration of blood flow in previous canine studies . We postulate that the cells have insufficient time to fully develop their attachment to the graft surface prior to exposure to hemodynamic stress. We allowed EC to incubate on fibronectin-coated ePTFE grafts for four different time periods after seeding and measured EC retention after perfusion in a canine ex vivo shunt circuit.Autologous canine EC, were enzymatically harvested, grown to confluence, and labeled with 30 μCi 111 Indium-oxine/80 cm 2 flask. Four groups of 5 cm x 4 mm ID ePTFE vascular prostheses were coated with 1.5 μg/cm.2 human fibronectin, and seeded with 1.5 x 105 EC/ cm.2. After seeding grafts in Group 1 were incubated in complete growth medium for 90 minutes, Group 2 were incubated for 24 hours, Group 3 for 72 hours and Group 4 for 6 days. Grafts were then placed in the canine ex vivo circuit, constructed between femoral artery and vein, and subjected to blood flow of 75 ml per minute for 6 hours. Continuous counting of γ-activity was made possible by placing the seeded graft inside the γ-counter detection crystal for the duration of perfusion. EC retention data after 30 minutes, 2 hours and 6 hours of flow are shown in the table.

In-vivo evaluation of the effect of cyanoacrylate on prosthetic vascular graft infection – does cyanoacrylate increase the severity of infection?

VASA ◽  
2020 ◽  
Vol 49 (4) ◽  
pp. 281-284
Author(s):  
Atıf Yolgosteren ◽  
Gencehan Kumtepe ◽  
Melda Payaslioglu ◽  
Cuneyt Ozakin
Keyword(s):  
Vascular Graft ◽  
Graft Infection ◽  
Vascular Graft Infection ◽  
Group 4 ◽  
Significant Difference ◽  
Group 3 ◽  
Group 2 ◽  
Prosthetic Vascular Graft Infection ◽  
Group 1

Summary. Background: Prosthetic vascular graft infection (PVGI) is a complication with high mortality. Cyanoacrylate (CA) is an adhesive which has been used in a number of surgical procedures. In this in-vivo study, we aimed to evaluate the relationship between PVGI and CA. Materials and methods: Thirty-two rats were equally divided into four groups. Pouch was formed on back of rats until deep fascia. In group 1, vascular graft with polyethyleneterephthalate (PET) was placed into pouch. In group 2, MRSA strain with a density of 1 ml 0.5 MacFarland was injected into pouch. In group 3, 1 cm 2 vascular graft with PET piece was placed into pouch and MRSA strain with a density of 1 ml 0.5 MacFarland was injected. In group 4, 1 cm 2 vascular graft with PET piece impregnated with N-butyl cyanoacrylate-based adhesive was placed and MRSA strain with a density of 1 ml 0.5 MacFarland was injected. All rats were scarified in 96th hour, culture samples were taken where intervention was performed and were evaluated microbiologically. Bacteria reproducing in each group were numerically evaluated based on colony-forming unit (CFU/ml) and compared by taking their average. Results: MRSA reproduction of 0 CFU/ml in group 1, of 1410 CFU/ml in group 2, of 180 200 CFU/ml in group 3 and of 625 300 CFU/ml in group 4 was present. A statistically significant difference was present between group 1 and group 4 (p < 0.01), between group 2 and group 4 (p < 0.01), between group 3 and group 4 (p < 0.05). In terms of reproduction, no statistically significant difference was found in group 1, group 2, group 3 in themselves. Conclusions: We observed that the rate of infection increased in the cyanoacyrylate group where cyanoacrylate was used. We think that surgeon should be more careful in using CA in vascular surgery.

Defensive activity of Hesperidin against Ciprofloxacin induced hepatic injury in rabbits.

2019 ◽  
Vol 10 (03) ◽  
Author(s):  
Hawraa M. Murad ◽  
Tamadhur Hani Hussein ◽  
Audai Sulaiman Khudhair ◽  
Manal Muhi Murad ◽  
Jawad Kadhim Faris
Keyword(s):  
Body Weight ◽  
Bacterial Infections ◽  
Hepatoprotective Activity ◽  
The Body ◽  
Local Breed ◽  
Group 4 ◽  
Group 3 ◽  
Group 2 ◽  
Defensive Activity ◽  
Antioxidant Effects

This study was conducted to find out hepatoprotective activity of hesperidin (HES) 100mg/kg body weight (b.w.) against ciprofloxacin (CPX) 100 mg/kg induced hepatotoxicity in local breed rabbits .CPX is a broad spectrum antibiotic used for treatment of many bacterial infections. Twenty four male rabbits were divided into four groups ,group1: control, (1 ml/kg Saline orally) group 2: CPX (100 mg/kg orally) for (14) consecutive days , group 3: HES (100 mg//kg) orally for (14) consecutive days group 4: CPX (100 mg/kg orally) plus HES (100 mg//kg orally ) for (14) consecutive days. All the rabbits were killed on the (15) day of the experiment, and then the blood, and livers samples were taken. CPX induced hepatotoxicity was proved by a significant (p less than 0.01) reduction in the body weight ,and a significant (p less than 0.01) increased serum aspartate transaminase (AST), alanine transaminase (ALT) , Malonaldehyde enzyme (MAD) and histopathological changes. Protective hepatic toxicity effect and oxidative damage caused by CPX significantly (p less than 0.01) increasing in body weight and significantly (p less than 0.01) decreasing AST , ALT, MAD and improving tissue morphology in HES (100 mg//kg) . These results assure that HES (100 mg//kg) antioxidant effects can protect CPX-induced hepatotoxicity in rabbits.

Does Perioperative Hemoglobin A1c Level Affect the Incidence, Pattern and Mortality of Lower Extremity Amputation?

2019 ◽  
Vol 17 (4) ◽  
pp. 354-364
Author(s):  
Hassan Al-Thani ◽  
Moamena El-Matbouly ◽  
Maryam Al-Sulaiti ◽  
Noora Al-Thani ◽  
Mohammad Asim ◽  
...  
Keyword(s):  
Glycemic Control ◽  
Lower Extremity ◽  
Hazard Ratio ◽  
Lower Extremity Amputation ◽  
Group 4 ◽  
Group 3 ◽  
Group 5 ◽  
Group 2 ◽  
Extremity Amputation ◽  
Group 1

Background: We hypothesized that perioperative HbA1c influenced the pattern and outcomes of Lower Extremity Amputation (LEA). Methods: A retrospective analysis was conducted for all patients who underwent LEA between 2000 and 2013. Patients were categorized into 5 groups according to their perioperative HbA1c values [Group 1 (<6.5%), Group 2 (6.5-7.4%), Group 3 (7.5-8.4%), Group 4 (8.5-9.4%) and Group 5 (≥9.5%)]. We identified 848 patients with LEA; perioperative HbA1c levels were available in 547 cases (Group 1: 18.8%, Group 2: 17.7%, Group 3: 15.0%, Group 4: 13.5% and Group 5: 34.9%). Major amputation was performed in 35%, 32%, 22%, 10.8% and 13.6%, respectively. Results: The overall mortality was 36.5%; of that one quarter occurred during the index hospitalization. Mortality was higher in Group 1 (57.4%) compared with Groups 2-5 (46.9%, 38.3%, 36.1% and 31.2%, respectively, p=0.001). Cox regression analysis showed that poor glycemic control (Group 4 and 5) had lower risk of mortality post-LEA [hazard ratio 0.57 (95% CI 0.35-0.93) and hazard ratio 0.46 (95% CI 0.31-0.69)]; this mortality risk persisted even after adjustment for age and sex but was statistically insignificant. The rate of LEA was greater among poor glycemic control patients; however, the mortality was higher among patients with tight control. Conclusion: The effects of HbA1c on the immediate and long-term LEA outcomes and its therapeutic implications need further investigation.

The Effects of the "XGTQ" Medicine in Treating Cirrhosis in Wistar Rats

2020 ◽  
Vol 06 ◽  
Author(s):  
Ngan Nguyen Hoang ◽  
Thang Duong Minh ◽  
Tuan Anh Hoang ◽  
Son Le Ngoc Bich ◽  
Duong Nguyen Huu ◽  
...  
Keyword(s):  
Wistar Rats ◽  
Reference Group ◽  
Control Group ◽  
Plain Water ◽  
Group 4 ◽  
White Rats ◽  
Collagen Accumulation ◽  
Activity Of Enzymes ◽  
Group 3 ◽  
Group 1

Objectives: Evaluate the effects of "XGTQ" in the treatment of cirrhosis induced by Carbon tetrachloride (CCL4) in combination with alcohol and high-fat diet on Wistar rats. Materials and methods: Cirrhosis on white rats was induced by subcutaneously injecting CC14 at an initial dose of 5,0ml/kg, followed by 1,2ml/kg once a week in 10 weeks. Then, fed with synthetic food, added 20% fat, and 0.05% cholesterol and iron oxalate. Rats were administered every day with plain water and 1 day with water mixed with 30% ethanol. The rats were randomly divided into 5 groups and given distilled water (group 1 and 2 or control group), silymarin (group 3 or reference group) or the "XGTQ" drug extract (group 4, 5) for 4 weeks. Collected blood for biochemical test and liver were dissected to evaluate weight, morphology and quantified 4-hydroxyproline to evaluate fibrosis and collagen accumulation. Results: In cirrhotic wistar rats, "XGTQ" drug at 19.6 g/kg/24h and 58.8 g/kg/24h showed the ability of reducing the activity of enzymes AST, ALT in the blood (p<0.01), increasing plasma albumin and decreasing prothrobin time (p<.05); improving physical condition, macroscopic and microscopic images of H&E-stained liver; decreasing the concentration of hydroxyproline in the liver and reducing the level of cirrhosis on the masson-stained templates. The effects of "XGTQ" increased with the dose, and was equivalent to silymarin at the dose of 70 mg/kg/24h. Conclusion: The extract of "XGTQ" drug is effective in treating cirrhosis in Wistar rats.

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