scholarly journals Differential CTCF binding in motor neurons and lymphocytes

2021 ◽  
Author(s):  
Belkis Atasever Arslan ◽  
Scott T. Brady ◽  
Gamze Gunal Sadik
Keyword(s):  
Gene Expression ◽  
Progenitor Cells ◽  
Motor Neurons ◽  
Neurological Disorders ◽  
Neural Progenitor Cells ◽  
Developmental Stages ◽  
Neural Progenitor ◽  
Ctcf Binding ◽  
Ctcf Binding Site ◽  
Expression Levels

Transcriptional regulation of protein-coding genes is a primary control mechanism of cellular function. Similarities in regulation of expression for select genes between lymphocytes and neurons have led to proposals that such genes may be useful biomarkers for some neurological disorders that can be monitored via patient lymphocyte populations. Examination of shared molecular mechanisms underlying neurogenesis and lymphocyte differentiation may give help to identify relevant pathways and suggest additional biomarkers in lymphocytes that are relevant to neurological disorders. In this study, we analysed similarities and conserved regions in several genes regulated by CCCTC-binding factor (CTCF) during lymphocyte and neuronal developmental stages. We performed epigenetic analysis of CTCF binding Trak1, Gabpa, Gabpb1, Gabpb2, Gfi1, Gfi1b gene loci at T and B lymphocytes at different developmental stages, as well as in neural progenitor cells and motor neurons. Common and shared CTCF binding events at Trak1 gene suggest additional transcriptional regulatory factors that control Trak1 gene expression levels differ in neurons and lymphocytes. Gabpb1 gene includes a common CTCF binding site shared with neurons and lymphocytes. Correlation of CTCF binding analysis and gene expression profile suggests that CTCF binding plays a role in epigenetic regulation of Gabpb1 gene. In contrast, while Gfi1a gene is phylogenetically well-conserved and CTCF sites are occupied in lymphocytes, there are no CTCF binding occupied in neurons and neural progenitor cells. Low expression levels of Gfi1s in neurons indicate that regulation of this gene is CTCF-independent in neurons. Although Gfi1b is highly homologous to Gfi1, differences in expression levels suggest that Gfi1b is critical for both lymphogenesis and neurogenesis. Neurons and lymphocytes have multiple common CTCF binding sites in the Gfi1b gene, although lineage specific transcriptional regulators that play a role in their different expression levels still need to be identified. The partial overlap in CTCF regulatory sites for some genes in neurons and lymphocytes suggest that there may be markers that can exhibit parallel changes in these cells and serve as biomarkers.

scholarly journals Differential CTCF binding in motor neurons and lymphocytes

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 708
Author(s):  
Belkis Atasever Arslan ◽  
Scott T. Brady ◽  
Gamze Gunal Sadik
Keyword(s):  
Gene Expression ◽  
Immune System ◽  
Progenitor Cells ◽  
Motor Neurons ◽  
Neural Progenitor Cells ◽  
Developmental Stages ◽  
Neural Progenitor ◽  
Ctcf Binding ◽  
Ctcf Binding Site ◽  
Expression Levels

Background: Diversity is critical to lymphocyte roles in the immune system and to neurons, which form complex network structures in the brain. Emerging evidence suggests that an increasing number of molecules associated with the immune system are also expressed in various central nervous system (CNS) regions and play crucial roles in brain development. Examination of shared molecular mechanisms underlying neurogenesis and lymphocyte differentiation may clarify relevant pathways, and suggests additional biomarkers in lymphocytes for neurological disorders. These results can contribute to find biomarkers that can be monitored through patient lymphocyte populations. Methods: We analysed similarities and conserved regions in several genes regulated by CCCTC-binding factor (CTCF) during lymphocyte and neuronal developmental stages. We performed epigenetic analyses of CTCF binding Trak1, Gabpa, Gabpb1, Gabpb2, Gfi1, Gfi1b gene loci in T and B lymphocytes at different developmental stages, as well as in neural progenitor cells and motor neurons. Results: Common and shared CTCF binding events at Trak1 suggest additional transcriptional regulatory factors that control Trak1 gene expression levels differ in neurons and lymphocytes. Gabpb1 includes a common CTCF binding site shared with neurons and lymphocytes. Correlation of CTCF binding analysis and gene expression profile suggests that CTCF binding plays a role in epigenetic regulation of Gabpb1 gene. While Gfi1a is phylogenetically well-conserved and CTCF sites are occupied in lymphocytes, there are no CTCF binding occupied in neurons and neural progenitor cells. Although Gfi1b is highly homologous to Gfi1, differences in expression levels suggest that Gfi1b is critical for both lymphogenesis and neurogenesis. Neurons and lymphocytes have multiple common CTCF binding sites in the Gfi1b gene. Conclusions: The partial overlap in CTCF regulatory sites for some genes in neurons and lymphocytes suggests that there may be markers which can exhibit parallel changes in these cells and serve as biomarkers.

scholarly journals Coxsackievirus B3 Infection of Human Neural Progenitor Cells Results in Distinct Expression Patterns of Innate Immune Genes

Viruses ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 325 ◽  
Author(s):  
Soo-Jin Oh ◽  
Jeong-An Gim ◽  
Jae Kyung Lee ◽  
Hosun Park ◽  
Ok Sarah Shin
Keyword(s):  
Gene Expression ◽  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Cellular Responses ◽  
Neural Progenitor ◽  
Coxsackievirus B3 ◽  
Type I ◽  
Expression Levels ◽  
Cvb3 Infection ◽  
Ifn Γ

Coxsackievirus B3 (CVB3), a member of Picornaviridae family, is an important human pathogen that causes a wide range of diseases, including myocarditis, pancreatitis, and meningitis. Although CVB3 has been well demonstrated to target murine neural progenitor cells (NPCs), gene expression profiles of CVB3-infected human NPCs (hNPCs) has not been fully explored. To characterize the molecular signatures and complexity of CVB3-mediated host cellular responses in hNPCs, we performed QuantSeq 3′ mRNA sequencing. Increased expression levels of viral RNA sensors (RIG-I, MDA5) and interferon-stimulated genes, such as IFN-β, IP-10, ISG15, OAS1, OAS2, Mx2, were detected in response to CVB3 infection, while IFN-γ expression level was significantly downregulated in hNPCs. Consistent with the gene expression profile, CVB3 infection led to enhanced secretion of inflammatory cytokines and chemokines, such as interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1). Furthermore, we show that type I interferon (IFN) treatment in hNPCs leads to significant attenuation of CVB3 RNA copy numbers, whereas, type II IFN (IFN-γ) treatment enhances CVB3 replication and upregulates suppressor of cytokine signaling 1/3 (SOCS) expression levels. Taken together, our results demonstrate the distinct molecular patterns of cellular responses to CVB3 infection in hNPCs and the pro-viral function of IFN-γ via the modulation of SOCS expression.

Proliferation deficits and gene expression dysregulation in Down's syndrome (Ts1Cje) neural progenitor cells cultured from neurospheres

2009 ◽  
Vol 87 (14) ◽  
pp. 3143-3152 ◽  
Author(s):  
Randal X. Moldrich ◽  
Luce Dauphinot ◽  
Julien Laffaire ◽  
Tania Vitalis ◽  
Yann Hérault ◽  
...  
Keyword(s):  
Gene Expression ◽  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Down's Syndrome ◽  
Down’S Syndrome ◽  
Neural Progenitor ◽  
Gene Expression Dysregulation ◽  
Cells Cultured

scholarly journals Transduction of human neural progenitor cells with foamy virus vectors for differentiation-dependent gene expression

Gene Therapy ◽  
2008 ◽  
Vol 16 (3) ◽  
pp. 349-358 ◽  
Author(s):  
I Rothenaigner ◽  
S Kramer ◽  
M Meggendorfer ◽  
A Rethwilm ◽  
R Brack-Werner
Keyword(s):  
Gene Expression ◽  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Foamy Virus ◽  
Neural Progenitor ◽  
Virus Vectors ◽  
Human Neural Progenitor Cells

scholarly journals Store-Operated CRAC Channels Regulate Gene Expression and Proliferation in Neural Progenitor Cells

2014 ◽  
Vol 34 (27) ◽  
pp. 9107-9123 ◽  
Author(s):  
A. Somasundaram ◽  
A. K. Shum ◽  
H. J. McBride ◽  
J. A. Kessler ◽  
S. Feske ◽  
...  
Keyword(s):  
Gene Expression ◽  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Regulate Gene Expression ◽  
Crac Channels ◽  
Regulate Gene

scholarly journals Downregulation of Neurodevelopmental Gene Expression in iPSC-Derived Cerebral Organoids Upon Infection by Human Cytomegalovirus

2021 ◽  
Author(s):  
Benjamin Shea O'Brien ◽  
Rebekah L Mokry ◽  
Megan L Schumacher ◽  
Kirthi Pulakanti ◽  
Sridhar Rao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Progenitor Cells ◽  
Human Cytomegalovirus ◽  
Neural Progenitor Cells ◽  
Treatment Options ◽  
Congenital Infection ◽  
Induced Pluripotent Stem Cell ◽  
Neural Progenitor ◽  
Human Neurons ◽  
The Impact

Human cytomegalovirus (HCMV) is a beta herpesvirus that, upon congenital infection, can cause severe birth defects including vision and hearing loss, microcephaly, and seizures. Currently, no approved treatment options exist for in utero infections. We previously demonstrated that HCMV infection decreases calcium signaling responses and alters neuronal differentiation in induced pluripotent stem cell (iPSC) derived neural progenitor cells (NPCs). Here we aimed to determine the impact of infection on the transcriptome in developing human neurons using iPSC-derived 3-dimensional cerebral organoids. We infected iPSC-derived cerebral organoids with HCMV encoding eGFP and sorted cell populations based on GFP signal strength. Significant transcriptional downregulation was observed including in key neurodevelopmental gene pathways in both the GFP (+) and intermediate groups. Interestingly, the GFP (-) group also showed downregulation of the same targets indicating a mismatch between GFP expression and viral infection. Using a modified HCMV virus destabilizing IE 1 and 2 proteins, we still observed significant downregulation of neurodevelopmental gene expression in infected neural progenitor cells. Together, these data indicate that IE viral proteins are not the main drivers of neurodevelopmental gene dysregulation in HCMV infected neural tissues suggesting therapeutically targeting IE gene expression is insufficient to restore neural differentiation and function.

Sign in / Sign up

Export Citation Format

Share Document