scholarly journals Neuronal Yin Yang1 in the prefrontal cortex regulates transcriptional and behavioral responses to chronic stress in mice

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Deborah Y. Kwon ◽  
Bing Xu ◽  
Peng Hu ◽  
Ying-Tao Zhao ◽  
Jonathan A. Beagan ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Transcriptome Profiling ◽  
Stress Sensitivity ◽  
Maladaptive Behavior ◽  
Chromatin Interactions ◽  
Selective Ablation ◽  
Excitatory Neurons ◽  
Transcriptional Changes ◽  
Single Nucleus ◽  
Cell Type Specific

AbstractAlthough the synaptic alterations associated with the stress-related mood disorder major depression has been well-documented, the underlying transcriptional mechanisms remain poorly understood. Here, we perform complementary bulk nuclei- and single-nucleus transcriptome profiling and map locus-specific chromatin interactions in mouse neocortex to identify the cell type-specific transcriptional changes associated with stress-induced behavioral maladaptation. We find that cortical excitatory neurons, layer 2/3 neurons in particular, are vulnerable to chronic stress and acquire signatures of gene transcription and chromatin structure associated with reduced neuronal activity and expression of Yin Yang 1 (YY1). Selective ablation of YY1 in cortical excitatory neurons enhances stress sensitivity in both male and female mice and alters the expression of stress-associated genes following an abbreviated stress exposure. These findings demonstrate how chronic stress impacts transcription in cortical excitatory neurons and identify YY1 as a regulator of stress-induced maladaptive behavior in mice.

scholarly journals Stress-induced epigenetic regulation of transcription in neocortical excitatory neurons drives depression-like behavior

2020 ◽  
Author(s):  
Deborah Y. Kwon ◽  
Peng Hu ◽  
Ying-Tao Zhao ◽  
Jonathan A. Beagan ◽  
Jonathan H. Nofziger ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Transcriptome Profiling ◽  
Stress Sensitivity ◽  
Maladaptive Behavior ◽  
Regulation Of Transcription ◽  
Stress Exposure ◽  
Excitatory Neurons ◽  
Chromatin Configuration ◽  
Single Nucleus ◽  
Cell Type Specific

ABSTRACTProlonged stress exposure is a major risk factor for the development of depression and comorbid anxiety. Efforts to understand how recurrent stress induces behavioral maladaptation have largely concentrated on the neuronal synapse with limited understanding of the underlying epigenetic mechanisms. Here, we performed complementary bulk nuclei- and single-nucleus transcriptome profiling and mapped fine-scale chromatin architecture in mice subjected to chronic unpredictable stress (CUS) to identify the cell type-specific epigenetic alterations that drive complex behavior. We find that neocortical excitatory neurons are particularly vulnerable to chronic stress and acquire signatures of transcription and chromatin configuration that denote reduced neuronal activity and expression of Yin Yang 1 (YY1). Selective ablation of YY1 in excitatory neurons of the prefrontal cortex (PFC) enhances stress sensitivity in mice, inducing depressive- and anxiety-related behaviors and deregulating the expression of stress-associated genes following an abbreviated stress exposure. Notably, we find that loss of YY1 in PFC excitatory neurons provokes more maladaptive behaviors in stressed females than males. These findings demonstrate how chronic stress provokes maladaptive behavior by epigenetically shaping excitatory neurons in the PFC, identifying a novel molecular target for therapeutic treatment of stress-related mood and anxiety disorders.

scholarly journals Single-cell transcriptomes of developing and adult olfactory receptor neurons in Drosophila

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Colleen N McLaughlin ◽  
Maria Brbić ◽  
Qijing Xie ◽  
Tongchao Li ◽  
Felix Horns ◽  
...  
Keyword(s):  
Single Cell ◽  
Developmental Stages ◽  
Sensory Modality ◽  
Olfactory Receptors ◽  
Receptor Expression ◽  
Transcriptional Changes ◽  
Single Nucleus ◽  
Cell Type Specific ◽  
Sensory Responses ◽  
And Function

Recognition of environmental cues is essential for the survival of all organisms. Transcriptional changes occur to enable the generation and function of the neural circuits underlying sensory perception. To gain insight into these changes, we generated single-cell transcriptomes of Drosophila olfactory- (ORNs), thermo-, and hygro-sensory neurons at an early developmental and adult stage using single-cell and single-nucleus RNA sequencing. We discovered that ORNs maintain expression of the same olfactory receptors across development. Using receptor expression and computational approaches, we matched transcriptomic clusters corresponding to anatomically and physiologically defined neuron types across multiple developmental stages. We found that cell-type-specific transcriptomes partly reflected axon trajectory choices in development and sensory modality in adults. We uncovered stage-specific genes that could regulate the wiring and sensory responses of distinct ORN types. Collectively, our data reveal transcriptomic features of sensory neuron biology and provide a resource for future studies of their development and physiology.

scholarly journals HiCRes: a computational method to estimate and predict the resolution of HiC libraries

2020 ◽  
Author(s):  
Claire Marchal ◽  
Nivedita Singh ◽  
Ximena Corso-Díaz ◽  
Anand Swaroop
Keyword(s):  
Expression Patterns ◽  
Three Dimensional ◽  
Computational Method ◽  
Mathematical Concepts ◽  
Regulate Gene Expression ◽  
Chromatin Interactions ◽  
Genome Wide ◽  
A Cell ◽  
Cell Type Specific ◽  
Human And Mouse

AbstractThree-dimensional (3D) conformation of the chromatin is crucial to stringently regulate gene expression patterns and DNA replication in a cell-type specific manner. HiC is a key technique for measuring 3D chromatin interactions genome wide. Estimating and predicting the resolution of a library is an essential step in any HiC experimental design. Here, we present the mathematical concepts to estimate the resolution of a library and predict whether deeper sequencing would enhance the resolution. We have developed HiCRes, a docker pipeline, by applying these concepts to human and mouse HiC libraries.

scholarly journals Mid and hindgut transcriptome profiling analysis of Atlantic salmon ( Salmon salar ) under unpredictable chronic stress

2020 ◽  
Vol 7 (2) ◽  
pp. 191480
Author(s):  
Signe Dille Løvmo ◽  
Angelico Madaro ◽  
Paul Whatmore ◽  
Tora Bardal ◽  
Mari-Ann Ostensen ◽  
...  
Keyword(s):  
Atlantic Salmon ◽  
Chronic Stress ◽  
Transcriptome Profiling ◽  
Intestinal Morphology ◽  
Differentially Expressed ◽  
Sequencing Analysis ◽  
Negative Consequences ◽  
Membrane Structures ◽  
Apoptotic Pathway ◽  
Salmon Parr

The intestinal epithelium is a selectively permeable barrier for nutrients, electrolytes and water, while maintaining effective protection against pathogens. Combinations of stressors throughout an animal's life, especially in agriculture and aquaculture settings, may affect the regular operativity of this organ with negative consequences for animal welfare. In the current study, we report the effects of a three-week unpredictable chronic stress (UCS) period on the intestinal morphology and transcriptome response of Atlantic salmon ( Salmon salar ) parr midgut and hindgut. Midgut and hindgut from both control and UCS fish were collected for histology and RNA-sequencing analysis to identify respective changes in the membrane structures and putative genes and pathways responding to UCS. Histological analysis did not show any significant effect on morphometric parameters. In the midgut, 1030 genes were differentially expressed following UCS, resulting in 279 genes which were involved in 13 metabolic pathways, including tissue repair pathways. In the hindgut, following UCS, 591 differentially expressed genes were detected with 426 downregulated and 165 upregulated. A total of 53 genes were related to three pathways. Downregulated genes include cellular senescence pathways, p53 signalling and cytokine–cytokine receptor pathways. The overall results corroborate that salmon parr were at least partly habituating to the UCS treatment. In midgut, the main upregulation was related to cell growth and repair, while in the hindgut there were indications of the activated apoptotic pathway, reduced cell repair and inhibited immune/anti-inflammatory capacity. This may be the trade-off between habituating to UCS and health resilience. This study suggests possible integrated genetic regulatory mechanisms that are tuned when farmed Atlantic salmon parr attempt to cope with UCS.

scholarly journals Single-nucleus transcriptome analysis reveals dysregulation of angiogenic endothelial cells and neuroprotective glia in Alzheimer’s disease

2020 ◽  
Vol 117 (41) ◽  
pp. 25800-25809 ◽  
Author(s):  
Shun-Fat Lau ◽  
Han Cao ◽  
Amy K. Y. Fu ◽  
Nancy Y. Ip
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Endothelial Cells ◽  
Transcriptome Analysis ◽  
Cell Type ◽  
Angiogenic Growth Factors ◽  
Cellular Targets ◽  
Therapeutic Development ◽  
Single Nucleus ◽  
Cell Type Specific

Alzheimer’s disease (AD) is the most common form of dementia but has no effective treatment. A comprehensive investigation of cell type-specific responses and cellular heterogeneity in AD is required to provide precise molecular and cellular targets for therapeutic development. Accordingly, we perform single-nucleus transcriptome analysis of 169,496 nuclei from the prefrontal cortical samples of AD patients and normal control (NC) subjects. Differential analysis shows that the cell type-specific transcriptomic changes in AD are associated with the disruption of biological processes including angiogenesis, immune activation, synaptic signaling, and myelination. Subcluster analysis reveals that compared to NC brains, AD brains contain fewer neuroprotective astrocytes and oligodendrocytes. Importantly, our findings show that a subpopulation of angiogenic endothelial cells is induced in the brain in patients with AD. These angiogenic endothelial cells exhibit increased expression of angiogenic growth factors and their receptors (i.e.,EGFL7,FLT1, andVWF) and antigen-presentation machinery (i.e.,B2MandHLA-E). This suggests that these endothelial cells contribute to angiogenesis and immune response in AD pathogenesis. Thus, our comprehensive molecular profiling of brain samples from patients with AD reveals previously unknown molecular changes as well as cellular targets that potentially underlie the functional dysregulation of endothelial cells, astrocytes, and oligodendrocytes in AD, providing important insights for therapeutic development.

scholarly journals Nap1l2 Promotes Histone Acetylation Activity during Neuronal Differentiation

2007 ◽  
Vol 27 (17) ◽  
pp. 6093-6102 ◽  
Author(s):  
Mikaël Attia ◽  
Christophe Rachez ◽  
Antoine De Pauw ◽  
Philip Avner ◽  
Ute Christine Rogner
Keyword(s):  
Histone Acetylation ◽  
Neuronal Differentiation ◽  
Nucleosome Assembly ◽  
Cell Type ◽  
Cell Stage ◽  
Transcriptional Changes ◽  
Cell Type Specific ◽  
Mediate Cell ◽  
Developing Neurons ◽  
Assembly Proteins

ABSTRACT The deletion of the neuronal Nap1l2 (nucleosome assembly protein 1-like 2) gene in mice causes neural tube defects. We demonstrate here that this phenotype correlates with deficiencies in differentiation and increased maintenance of the neural stem cell stage. Nap1l2 associates with chromatin and interacts with histones H3 and H4. Loss of Nap1l2 results in decreased histone acetylation activity, leading to transcriptional changes in differentiating neurons, which include the marked downregulation of the Cdkn1c (cyclin-dependent kinase inhibitor 1c) gene. Cdkn1c expression normally increases during neuronal differentiation, and this correlates with the specific recruitment of the Nap1l2 protein and an increase in acetylated histone H3K9/14 at the site of Cdkn1c transcription. These results lead us to suggest that the Nap1l2 protein plays an important role in regulating transcription in developing neurons via the control of histone acetylation. Our data support the idea that neuronal nucleosome assembly proteins mediate cell-type-specific mechanisms of establishment/modification of a chromatin-permissive state that can affect neurogenesis and neuronal survival.

scholarly journals Single-nucleus RNA-seq reveals dysregulation of striatal cell identity due to Huntington’s disease mutations

2020 ◽  
Author(s):  
Sonia Malaiya ◽  
Marcia Cortes-Gutierrez ◽  
Brian R. Herb ◽  
Sydney R. Coffey ◽  
Samuel R.W. Legg ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neurodegenerative Disorder ◽  
Cell Types ◽  
Transcriptional Networks ◽  
Rna Seq ◽  
Cell Type ◽  
Cell Identity ◽  
Transcriptional Changes ◽  
Cell Type Specific

ABSTRACTHuntington’s disease (HD) is a dominantly inherited neurodegenerative disorder caused by a trinucleotide expansion in exon 1 of the huntingtin (Htt) gene. Cell death in HD occurs primarily in striatal medium spiny neurons (MSNs), but the involvement of specific MSN subtypes and of other striatal cell types remains poorly understood. To gain insight into cell type-specific disease processes, we studied the nuclear transcriptomes of 4,524 cells from the striatum of a genetically precise knock-in mouse model of the HD mutation, HttQ175/+, and from wildtype controls. We used 14-15-month-old mice, a time point roughly equivalent to an early stage of symptomatic human disease. Cell type distributions indicated selective loss of D2 MSNs and increased microglia in aged HttQ175/+ mice. Thousands of differentially expressed genes were distributed across most striatal cell types, including transcriptional changes in glial populations that are not apparent from RNA-seq of bulk tissue. Reconstruction of cell typespecific transcriptional networks revealed a striking pattern of bidirectional dysregulation for many cell type-specific genes. Typically, these genes were repressed in their primary cell type, yet de-repressed in other striatal cell types. Integration with existing epigenomic and transcriptomic data suggest that partial loss-of-function of the Polycomb Repressive Complex 2 (PRC2) may underlie many of these transcriptional changes, leading to deficits in the maintenance of cell identity across virtually all cell types in the adult striatum.

scholarly journals Neocortical layer 4 in adult mouse differs in major cell types and circuit organization between primary sensory areas

2018 ◽  
Author(s):  
F. Scala ◽  
D. Kobak ◽  
S. Shan ◽  
Y. Bernaerts ◽  
S. Laturnus ◽  
...  
Keyword(s):  
Adult Mouse ◽  
Building Blocks ◽  
Cell Types ◽  
Excitatory Input ◽  
Excitatory Neurons ◽  
Layer 4 ◽  
Cell Type Specific ◽  
Fast Spiking ◽  
Mouse Visual Cortex ◽  
Whole Cell Recordings

AbstractLayer 4 (L4) of mammalian neocortex plays a crucial role in cortical information processing, yet a complete census of its cell types and connectivity remains elusive. Using whole-cell recordings with morphological recovery, we identified one major excitatory and seven inhibitory types of neurons in L4 of adult mouse visual cortex (V1). Nearly all excitatory neurons were pyramidal and all somatostatin-positive (SOM+) non-fast-spiking neurons were Martinotti cells. In contrast, in somatosensory cortex (S1), excitatory neurons were mostly stellate and SOM+ neurons were non-Martinotti. These morphologically distinct SOM+ interneurons corresponded to different transcriptomic cell types and were differentially integrated into the local circuit with only S1 neurons receiving local excitatory input. We propose that cell-type specific circuit motifs, such as the Martinotti/pyramidal and non-Martinotti/stellate pairs, are optionally used across the cortex as building blocks to assemble cortical circuits.

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