System for Simultaneous Tissue-Specific and Disease-Specific Regulation of Therapeutic Gene Expression

2003 ◽  
Vol 14 (13) ◽  
pp. 1255-1264 ◽  
Author(s):  
Yung H. Chyung ◽  
Peter D. Peng ◽  
Mark A. Kay
2020 ◽  
Author(s):  
Shufa Yang ◽  
Chenghong Yin ◽  
Yan Liu ◽  
Taifeng Zhuang

Abstract BackgroundHuman amniotic fluid (AF) cells are commonly used in prenatal diagnosis. The AF cell-free mRNA (cfRNA) derived from necrotic or apoptotic cells of fetus may provide feasible marker of organ development and fetal malformation. Analysis of gene co-expression network will help to annotate AF cfRNA gene variations in fetal diseases.MethodsDatasets of amniotic fluid free RNA were downloaded from the Gene Expression Omnibus database. Co-expressed modules based on normal fetus AF cfRNA transcriptome were established via Weighted Gene Co-expression Network Analysis. The relationship between modules and tissues were set up via tissue-specific gene expression analysis of genes in modules. Differential expressed genes in Down syndrome (DS), Edwards syndrome (ES), and Turner syndrome (TS) were analyzed via linear models implemented in the limma package. Gene Ontology (GO) analysis of modular specific differential expressed genes for these three syndrome fetus was performed separately. Based on relationship of GO terms, GO graph of all enriched GO terms were constructed. The associated enriched GO terms in GO graph were considered as the same subset. Numbers of GO terms of the same subset with diseases and modules were calculated.ResultsA total of 22 co-expressed modules were constructed. Most of co-expressed module eigengenes showed no correlation with gestation weeks. Probe sets with higher expression values showed significant clustering tendencies. Dominant tissues and modules were different for different modules and tissues respectively through analysis of tissue-specific genes distribution in modules. The total numbers of enriched GO terms in six major modules were related to diseases severity for ES, DS, and TS. Disease-specific modules for ES, DS, and TS were detected in relation to biological processes through GO analysis. Differential expressed genes in disease-specific module were identified for DS, ES, and TS.ConclusionsThe gene co-expression network for functional classification provides a potential tool for annotating AF cfRNA variations in fetal diseases.


1992 ◽  
Vol 112 (2) ◽  
pp. 175-182 ◽  
Author(s):  
Masazumi Tada ◽  
Saori Takahashi ◽  
Motoshige Miyano ◽  
Yoshihiro Miyake

2013 ◽  
Vol 40 (12) ◽  
pp. 6685-6690 ◽  
Author(s):  
Lyudmila V. Dergunova ◽  
Alexandra V. Rozhkova ◽  
Olga Yu. Sudarkina ◽  
Svetlana A. Limborska

2011 ◽  
Vol 29 ◽  
pp. e144
Author(s):  
K. Guske ◽  
M. Herrmann ◽  
M. Schelleckes ◽  
B. Schmitz ◽  
K. Duning ◽  
...  

2004 ◽  
Vol 286 (6) ◽  
pp. R977-R988 ◽  
Author(s):  
Joachim Fandrey

Hypoxia-inducible expression of the gene encoding for the glycoprotein hormone erythropoietin (EPO) is the paradigm of oxygen-regulated gene expression. EPO is the main regulator of red blood cell production and more than 100 years of research on the regulation of EPO production have led to the identification of a widespread cellular oxygen sensing mechanism. Central to this signaling cascade is the transcription factor complex hypoxia-inducible factor-1 (HIF-1). Meanwhile, it is known that HIF-1 controls more than 50 oxygen-dependent genes and is now recognized as the main regulator of oxygen homoeostasis in the body. In addition to hypoxic induction, expression of the EPO gene is tightly regulated in a tissue-specific manner. During ontogeny, production of EPO required for erythropoiesis is switched from the fetal liver to the kidneys. Here EPO is mainly synthesized in adulthood. Production of EPO has also been found in organs where it has nonerythropoietic functions: EPO is important for development of the brain and is neuroprotective, whereas it stimulates angiogenesis in the reproductive tract and possibly in other organs. Understanding oxygen and tissue-specific regulation of EPO production is of high relevance for physiology. Moreover, this knowledge might be useful for new therapies to treat human diseases.


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