scholarly journals Cell Type-Specific Role of RNA Nuclease SMG6 in Neurogenesis

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3365
Author(s):  
Gabriela Maria Guerra ◽  
Doreen May ◽  
Torsten Kroll ◽  
Philipp Koch ◽  
Marco Groth ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Fate ◽  
Cortical Neurons ◽  
Embryonic Stem ◽  
Normal Structure ◽  
Mutant Mice ◽  
Cell Type ◽  
Nonsense Mediated Mrna Decay ◽  
A Cell ◽  
Cell Type Specific

SMG6 is an endonuclease, which cleaves mRNAs during nonsense-mediated mRNA decay (NMD), thereby regulating gene expression and controling mRNA quality. SMG6 has been shown as a differentiation license factor of totipotent embryonic stem cells. To investigate whether it controls the differentiation of lineage-specific pluripotent progenitor cells, we inactivated Smg6 in murine embryonic neural stem cells. Nestin-Cre-mediated deletion of Smg6 in mouse neuroprogenitor cells (NPCs) caused perinatal lethality. Mutant mice brains showed normal structure at E14.5 but great reduction of the cortical NPCs and late-born cortical neurons during later stages of neurogenesis (i.e., E18.5). Smg6 inactivation led to dramatic cell death in ganglionic eminence (GE) and a reduction of interneurons at E14.5. Interestingly, neurosphere assays showed self-renewal defects specifically in interneuron progenitors but not in cortical NPCs. RT-qPCR analysis revealed that the interneuron differentiation regulators Dlx1 and Dlx2 were reduced after Smg6 deletion. Intriguingly, when Smg6 was deleted specifically in cortical and hippocampal progenitors, the mutant mice were viable and showed normal size and architecture of the cortex at E18.5. Thus, SMG6 regulates cell fate in a cell type-specific manner and is more important for neuroprogenitors originating from the GE than for progenitors from the cortex.

United colours of chromatin? Developmental genome organisation in flies

2019 ◽  
Vol 47 (2) ◽  
pp. 691-700
Author(s):  
Caroline Delandre ◽  
Owen J. Marshall
Keyword(s):  
Cell Fate ◽  
Fruit Fly ◽  
Genome Organisation ◽  
Chromatin Protein ◽  
Cell Type ◽  
Chromatin States ◽  
Cell Fate Decisions ◽  
A Cell ◽  
Cell Type Specific ◽  
Chromatin Biology

Abstract The organisation of DNA into differing forms of packaging, or chromatin, controls many of the cell fate decisions during development. Although early studies focused on individual forms of chromatin, in the last decade more holistic studies have attempted to determine a complete picture of the different forms of chromatin present within a cell. In the fruit fly, Drosophila melanogaster, the study of chromatin states has been aided by the use of complementary and cell-type-specific techniques that profile the marks that recruit chromatin protein binding or the proteins themselves. Although many questions remain unanswered, a clearer picture of how different chromatin states affect development is now emerging, with more unusual chromatin states such as Black chromatin playing key roles. Here, we discuss recent findings regarding chromatin biology in flies.

scholarly journals ProNGF Is a Cell-Type-Specific Mitogen for Adult Hippocampal and for Induced Neural Stem Cells

Stem Cells ◽  
2019 ◽  
Vol 37 (9) ◽  
pp. 1223-1237 ◽  
Author(s):  
Valerio Corvaglia ◽  
Domenica Cilli ◽  
Chiara Scopa ◽  
Rossella Brandi ◽  
Ivan Arisi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Cell Type ◽  
A Cell ◽  
Cell Type Specific ◽  
Induced Neural Stem Cells

STAT3 is required for proliferation and exhibits a cell type-specific binding preference in mouse female germline stem cells

2018 ◽  
Vol 14 (2) ◽  
pp. 95-102 ◽  
Author(s):  
Yunzhao Gu ◽  
Jun Wu ◽  
Wenxiao Yang ◽  
Chao Xia ◽  
Xinglong Shi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Specific Binding ◽  
Binding Pattern ◽  
Germline Stem Cells ◽  
Cell Type ◽  
Stat3 Signaling ◽  
Binding Preference ◽  
A Cell ◽  
Cell Type Specific ◽  
Female Germline

LIF-mediated STAT3 signaling contributes to proliferation and exhibits a cell-specific binding pattern in mouse female germline stem cells.

Cell-type-specific consequences of nucleotide excision repair deficiencies: Embryonic stem cells versus fibroblasts

DNA Repair ◽  
2008 ◽  
Vol 7 (10) ◽  
pp. 1659-1669 ◽  
Author(s):  
H DEWAARD ◽  
E SONNEVELD ◽  
J DEWIT ◽  
R LANGE ◽  
J HOEIJMAKERS ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Embryonic Stem ◽  
Cell Type ◽  
Nucleotide Excision ◽  
Cell Type Specific

scholarly journals Total Functional Score of Enhancer Elements Identifies Lineage-Specific Enhancers That Drive Differentiation of Pancreatic Cells

2020 ◽  
Vol 14 ◽  
pp. 117793222093806
Author(s):  
Venkat S. Malladi ◽  
Anusha Nagari ◽  
Hector L Franco ◽  
W Lee Kraus
Keyword(s):  
Stem Cells ◽  
Embryonic Stem ◽  
Functional Score ◽  
Cell Type ◽  
Computational Framework ◽  
Genomic Data Integration ◽  
Genomic Assays ◽  
Pancreatic Cells ◽  
Cell Type Specific ◽  
Calling Algorithm

The differentiation of embryonic stem cells into various lineages is highly dependent on the chromatin state of the genome and patterns of gene expression. To identify lineage-specific enhancers driving the differentiation of progenitors into pancreatic cells, we used a previously described computational framework called Total Functional Score of Enhancer Elements (TFSEE), which integrates multiple genomic assays that probe both transcriptional and epigenomic states. First, we evaluated and compared TFSEE as an enhancer-calling algorithm with enhancers called using GRO-seq-defined enhancer transcripts (method 1) versus enhancers called using histone modification ChIP-seq data (method 2). Second, we used TFSEE to define the enhancer landscape and identify transcription factors (TFs) that maintain the multipotency of a subpopulation of endodermal stem cells during differentiation into pancreatic lineages. Collectively, our results demonstrate that TFSEE is a robust enhancer-calling algorithm that can be used to perform multilayer genomic data integration to uncover cell type-specific TFs that control lineage-specific enhancers.

scholarly journals Differential transcriptional regulation of the NANOG gene in chicken primordial germ cells and embryonic stem cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hee Jung Choi ◽  
So Dam Jin ◽  
Deivendran Rengaraj ◽  
Jin Hwa Kim ◽  
Bertrand Pain ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcriptional Regulation ◽  
Embryonic Stem Cells ◽  
Germ Cells ◽  
Primordial Germ Cells ◽  
Embryonic Stem ◽  
Regulatory Elements ◽  
Cell Type ◽  
Transcriptional Regulatory ◽  
Cell Type Specific

Abstract Background NANOG is a core transcription factor (TF) in embryonic stem cells (ESCs) and primordial germ cells (PGCs). Regulation of the NANOG gene by TFs, epigenetic factors, and autoregulatory factors is well characterized in ESCs, and transcriptional regulation of NANOG is well established in these cells. Although NANOG plays a key role in germ cells, the molecular mechanism underlying its transcriptional regulation in PGCs has not been studied. Therefore, we investigated the mechanism that regulates transcription of the chicken NANOG (cNANOG) gene in PGCs and ESCs. Results We first identified the transcription start site of cNANOG by 5′-rapid amplification of cDNA ends PCR analysis. Then, we measured the promoter activity of various 5′ flanking regions of cNANOG in chicken PGCs and ESCs using the luciferase reporter assay. cNANOG expression required transcriptional regulatory elements, which were positively regulated by POU5F3 (OCT4) and SOX2 and negatively regulated by TP53 in PGCs. The proximal region of the cNANOG promoter contains a positive transcriptional regulatory element (CCAAT/enhancer-binding protein (CEBP)-binding site) in ESCs. Furthermore, small interfering RNA-mediated knockdown demonstrated that POU5F3, SOX2, and CEBP played a role in cell type-specific transcription of cNANOG. Conclusions We show for the first time that different trans-regulatory elements control transcription of cNANOG in a cell type-specific manner. This finding might help to elucidate the mechanism that regulates cNANOG expression in PGCs and ESCs.

scholarly journals Mammalian non-CG methylations are conserved and cell-type specific and may have been involved in the evolution of transposon elements

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Weilong Guo ◽  
Michael Q. Zhang ◽  
Hong Wu
Keyword(s):  
Stem Cells ◽  
Primordial Germ Cells ◽  
Embryonic Stem ◽  
Biological Significance ◽  
Prediction Method ◽  
Cell Types ◽  
Evolutionary Development ◽  
Cell Type ◽  
Brain Neurons ◽  
Cell Type Specific

Abstract Although non-CG methylations are abundant in several mammalian cell types, their biological significance is sparsely characterized. We gathered 51 human and mouse DNA methylomes from brain neurons, embryonic stem cells and induced pluripotent stem cells, primordial germ cells and oocytes. We utilized an unbiased sub-motif prediction method and reported CW as the representative non-CG methylation context, which is distinct from CC methylation in terms of sequence context and genomic distribution. A two-dimensional comparison of non-CG methylations across cell types and species was performed. Unambiguous studies of sequence preferences and genomic region enrichment showed that CW methylation is cell-type specific and is also conserved between humans and mice. In brain neurons, it was found that active long interspersed nuclear element-1 (LINE-1) lacked CW methylations but not CG methylations. Coincidentally, both human Alu and mouse B1 elements preferred high CW methylations at specific loci during their respective evolutionary development. Last, the strand-specific distributions of CW methylations in introns and long interspersed nuclear elements are also cell-type specific and conserved. In summary, our results illustrate that CW methylations are highly conserved among species, are dynamically regulated in each cell type, and are potentially involved in the evolution of transposon elements.

scholarly journals Cannabinoid type 2 receptors mediate a cell type-specific self-inhibition in cortical neurons

2018 ◽  
Vol 139 ◽  
pp. 217-225 ◽  
Author(s):  
Alexander Stumpf ◽  
Daniel Parthier ◽  
Rosanna P. Sammons ◽  
A. Vanessa Stempel ◽  
Jörg Breustedt ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Cell Type ◽  
A Cell ◽  
Cell Type Specific

scholarly journals Transcriptional regulation of schizophrenia risk gene TCF4 in inhibitory neurons during neurodevelopment

2021 ◽  
Author(s):  
yuanyuan wang ◽  
mingyan lin
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Regulatory Networks ◽  
Embryonic Stem ◽  
Inhibitory Neurons ◽  
Dependent Manner ◽  
Cell Type ◽  
Risk Gene ◽  
Cell Type Specific ◽  
Cell Transcriptome

The pathology underlying schizophrenia (SCZ) involves cell type-specific and developmental stage-specific dysregulation of multiple gene regulatory networks dominated by some key transcription factors, such as SCZ risk gene transcription factor 4 (TCF4). Previous studies on the regulatory mechanism of TCF4 use SY5Y as the cellular model, which could not reflect its cell type-specific role in the real world. Using the transcriptional profile of whole brain during development stages and single-cell transcriptome data in the developing human prefrontal cortex, we found that TCF4 was preferentially expressed in the interneuron. Chromatin immunoprecipitation combined with sequencing (ChIP-Seq) in human embryonic stem cells (hESC)-derived interneurons revealed that TCF4 primarily activate transcription of genes associated with cortex development and telencephalon regionalization in a long-range manner. As expected, the downstream targets of TCF4 were distinct in inhibitory neurons and neural stem cells during early neurodevelopment, justifying the importance of our study. Deeper investigation further revealed that TCF4 regulate genes related to neurotransmission distally in interneuron in a c-FOS dependent manner, while TCF4 and TCF3 synergistically regulate genes associated with cell proliferation associated proximally in neural stem cells. Our findings suggested that defects in development of interneuron, for instance as a result of TCF4 abnormality, may break excitation and inhibition balance and contribute significantly to the risk of SCZ.

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