Modelling functional differentiation and function loss

1990 ◽  
pp. 337 ◽  
Author(s):  
Terttu Nevalainen
Keyword(s):  
Functional Differentiation ◽  
Function Loss ◽  
And Function

scholarly journals T-BET and EOMES Accelerate and Enhance Functional Differentiation of Human Natural Killer Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Laura Kiekens ◽  
Wouter Van Loocke ◽  
Sylvie Taveirne ◽  
Sigrid Wahlen ◽  
Eva Persyn ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Cell Biology ◽  
Nk Cell ◽  
Current Knowledge ◽  
Functional Differentiation ◽  
Cell Maturation ◽  
Hematopoietic Stem ◽  
And Function

T-bet and Eomes are transcription factors that are known to be important in maturation and function of murine natural killer (NK) cells. Reduced T-BET and EOMES expression results in dysfunctional NK cells and failure to control tumor growth. In contrast to mice, the current knowledge on the role of T-BET and EOMES in human NK cells is rudimentary. Here, we ectopically expressed either T-BET or EOMES in human hematopoietic progenitor cells. Combined transcriptome, chromatin accessibility and protein expression analyses revealed that T-BET or EOMES epigenetically represses hematopoietic stem cell quiescence and non-NK lineage differentiation genes, while activating an NK cell-specific transcriptome and thereby drastically accelerating NK cell differentiation. In this model, the effects of T-BET and EOMES are largely overlapping, yet EOMES shows a superior role in early NK cell maturation and induces faster NK receptor and enhanced CD16 expression. T-BET particularly controls transcription of terminal maturation markers and epigenetically controls strong induction of KIR expression. Finally, NK cells generated upon T-BET or EOMES overexpression display improved functionality, including increased IFN-γ production and killing, and especially EOMES overexpression NK cells have enhanced antibody-dependent cellular cytotoxicity. Our findings reveal novel insights on the regulatory role of T-BET and EOMES in human NK cell maturation and function, which is essential to further understand human NK cell biology and to optimize adoptive NK cell therapies.

scholarly journals H19 lncRNA alters methylation and expression of Hnf4α in the liver of metformin-exposed fetuses

2017 ◽  
Vol 8 (12) ◽  
pp. e3175-e3175 ◽  
Author(s):  
Jie Deng ◽  
Martin Mueller ◽  
Tingting Geng ◽  
Yuanyuan Shen ◽  
Ya Liu ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Animal Studies ◽  
Fetal Liver ◽  
Functional Differentiation ◽  
Regulation Of Expression ◽  
Adenosylhomocysteine Hydrolase ◽  
Human Liver Cell ◽  
Key Factor ◽  
Mouse Fetuses ◽  
And Function

Abstract Metformin is the most widely used anti-diabetic medication worldwide. However, human and animal studies suggest that prenatal metformin exposure may increase the risk of metabolic disorders in adult offspring, yet the underpinning mechanism remains unclear. Here we report that metformin-exposed mouse fetuses exhibit elevated expression of the H19 long noncoding RNA, which induces hypomethylation and increased expression of hepatocyte nuclear factor 4α (HNF4α). As a transcription factor essential for morphological and functional differentiation of hepatocytes, HNF4α also has an indispensable role in the regulation of expression of gluconeogenic genes. Consistently, H19 overexpression in a human liver cell line leads to decreased methylation and increased expression of Hnf4α, with concomitant activation of the gluconeogenic program. Mechanistically, we show that the methylation change of Hnf4α is induced by H19-mediated regulation of S-adenosylhomocysteine hydrolase. We also provide evidence that altered H19 expression is a direct effect of metformin in the fetal liver. Our results suggest that metformin from the mother can directly act upon the fetal liver to modify Hnf4α expression, a key factor for both liver development and function, and that perturbation of this H19/Hnf4α-mediated pathway may contribute to the fetal origin of adult metabolic abnormalities.

Comparison between Tc-99m DMSA and Renal Ultrasonography for the Evaluation of Renal Scarring and Function Loss in Children with Spina Bifida

2017 ◽  
Vol 18 (2) ◽  
pp. 76-79
Author(s):  
Ebru Ozgonenel ◽  
Isik Karalok ◽  
Emel Ceylan Gunay ◽  
Tomris Duymaz ◽  
Ibrahim Alatas ◽  
...  
Keyword(s):  
Spina Bifida ◽  
Renal Scarring ◽  
Renal Ultrasonography ◽  
Function Loss ◽  
And Function

scholarly journals Extensive Expansion of the Speedy gene Family in Homininae and Functional Differentiation in Humans

2018 ◽  
Author(s):  
Liang Wang ◽  
Hui Wang ◽  
Hongmei Wang ◽  
Yuhui Zhao ◽  
Xiaojun Liu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Gene Family ◽  
Gene Networks ◽  
Functional Differentiation ◽  
Cell Cycles ◽  
Cycle Plays ◽  
Eukaryotic Species ◽  
Regulation Network ◽  
Cancer Types ◽  
And Function

AbstractBackgroundThe cell cycle plays important roles in physiology and disease. The Speedy/RINGO family of atypical cyclins regulates the cell cycle. However, the origin, evolution and function of the Speedy family are not completely understood. Understanding the origins and evolution of Speedy family would shed lights on the evolution of complexity of cell cycles in eukaryotes.ResultsHere, we performed a comprehensive identification of Speedy genes in 258 eukaryotic species and found that the Speedy subfamily E was extensively expanded in Homininae, characterized by emergence of a low-Spy1-identify domain. Furthermore, the Speedy gene family show functional differentiation in humans and have a distinct expression pattern, different regulation network and co-expressed gene networks associated with cell cycle and various signaling pathways. Expression levels of the Speedy gene family are prognostic biomarkers among different cancer types.ConclusionsOverall, we present a comprehensive view of the Speedy genes and highlight their potential function.

Unique XCI evolution in Tokudaia: initial XCI of the neo-X chromosome in Tokudaia muenninki and function loss of XIST in Tokudaia osimensis

Chromosoma ◽  
2017 ◽  
Vol 126 (6) ◽  
pp. 741-751 ◽  
Author(s):  
Hideki Zushi ◽  
Chie Murata ◽  
Shusei Mizushima ◽  
Chizuko Nishida ◽  
Asato Kuroiwa
Keyword(s):  
X Chromosome ◽  
Function Loss ◽  
And Function

scholarly journals Oxygenation of the Intraportally Transplanted Pancreatic Islet

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Thomas M. Suszynski ◽  
Efstathios S. Avgoustiniatos ◽  
Klearchos K. Papas
Keyword(s):  
Volume Fraction ◽  
Islet Cells ◽  
Thrombus Formation ◽  
Reaction Model ◽  
Diffusion Reaction ◽  
Loss Of Function ◽  
Islet Volume ◽  
Function Loss ◽  
Average Size ◽  
And Function

Intraportal islet transplantation (IT) is not widely utilized as a treatment for type 1 diabetes. Oxygenation of the intraportally transplanted islet has not been studied extensively. We present a diffusion-reaction model that predicts the presence of ananoxiccore and a largerpartly functionalcore within intraportally transplanted islets. Four variables were studied: islet diameter, islet fractional viability, external oxygen partial pressure (P) (in surrounding portal blood), and presence or absence of a thrombus on the islet surface. Results indicate that an islet with average size and fractional viability exhibits an anoxic volume fraction (AVF) of 14% and a function loss of 72% at a low externalP. Thrombus formation increased AVF to 30% and function loss to 92%, suggesting that the effect of thrombosis may be substantial. ExternalPand islet diameter accounted for the greatest overall impact on AVF and loss of function. At our institutions, large human alloislets (>200μm diameter) account for ~20% of total islet number but ~70% of total islet volume; since most of the total transplanted islet volume is accounted for by large islets, most of the intraportal islet cells are likely to be anoxic and not fully functional.

scholarly journals Urocortin II Treatment Reduces Skeletal Muscle Mass and Function Loss During Atrophy and Increases Nonatrophying Skeletal Muscle Mass and Function

Endocrinology ◽  
2003 ◽  
Vol 144 (11) ◽  
pp. 4939-4946 ◽  
Author(s):  
Richard T. Hinkle ◽  
Elizabeth Donnelly ◽  
David B. Cody ◽  
Mary Beth Bauer ◽  
Robert J. Isfort
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Function Loss ◽  
And Function

scholarly journals Circular RNA CREBBP Suppresses Hepatic Fibrosis Via Targeting the hsa-miR-1291/LEFTY2 Axis

2021 ◽  
Vol 12 ◽  
Author(s):  
Ya-Ru Yang ◽  
Shuang Hu ◽  
Fang-Tian Bu ◽  
Hao Li ◽  
Cheng Huang ◽  
...  
Keyword(s):  
Hepatic Fibrosis ◽  
Circular Rna ◽  
Vehicle Group ◽  
Potential Biomarker ◽  
Function Loss ◽  
And Function ◽  
Pro Inflammatory Cytokines

CircRNAs (circRNAs) are commonly dysregulated in a variety of human diseases and are involved in the development and progression of cancer. However, the role of circRNAs in hepatic fibrosis (HF) is still unclear. Our previous high throughput screen revealed changes in many circRNAs in mice with carbon tetrachloride (CCl4)-induced HF. For example, circCREBBP was significantly down-regulated in primary hepatic stellate cells (HSCs) and liver tissue of HF mice induced by CCl4 compared to those in the vehicle group. Overexpression of circCREBBP with AAV8-circCREBBP in vivo prevented CCl4-induced HF worsening by reducing serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) contents, liver hydroxyproline levels, collagen deposition, and levels of pro-fibrosis genes and pro-inflammatory cytokines. Furthermore, in vitro function loss and function gain analysis showed that circCREBBP inhibited HSCs activation and proliferation. Mechanically, circCREBBP acts as a sponge for hsa-miR-1291 and subsequently promotes LEFTY2 expression. In conclusion, our current results reveal a novel mechanism by which circCREBBP alleviates liver fibrosis by targeting the hsa-miR-1291/LEFTY2 axis, and also suggest that circCREBBP may be a potential biomarker for heart failure.

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