scholarly journals The centrosome neither persistently leads migration nor determines the site of axonogenesis in migrating neurons in vivo

2010 ◽  
Vol 191 (4) ◽  
pp. 875-890 ◽  
Author(s):  
Martin Distel ◽  
Jennifer C. Hocking ◽  
Katrin Volkmann ◽  
Reinhard W. Köster
Keyword(s):  
Gene Expression ◽  
Neuronal Migration ◽  
Cell Type ◽  
Vertebrate Brain ◽  
Cell Type Specific ◽  
Positive Correlations ◽  
Experimental Findings ◽  
Rhombic Lip

The position of the centrosome ahead of the nucleus has been considered crucial for coordinating neuronal migration in most developmental situations. The proximity of the centrosome has also been correlated with the site of axonogenesis in certain differentiating neurons. Despite these positive correlations, accumulating experimental findings appear to negate a universal role of the centrosome in determining where an axon forms, or in leading the migration of neurons. To further examine this controversy in an in vivo setting, we have generated cell type–specific multi-cistronic gene expression to monitor subcellular dynamics in the developing zebrafish cerebellum. We show that migration of rhombic lip–derived neurons is characterized by a centrosome that does not persistently lead the nucleus, but which is instead regularly overtaken by the nucleus. In addition, axonogenesis is initiated during the onset of neuronal migration and occurs independently of centrosome proximity. These in vivo data reveal a new temporal orchestration of organelle dynamics and provide important insights into the variation in intracellular processes during vertebrate brain differentiation.

scholarly journals Revisiting the role of IRF3 in inflammation and immunity by conditional and specifically targeted gene ablation in mice

2018 ◽  
Vol 115 (20) ◽  
pp. 5253-5258 ◽  
Author(s):  
Hideyuki Yanai ◽  
Shiho Chiba ◽  
Sho Hangai ◽  
Kohei Kometani ◽  
Asuka Inoue ◽  
...  
Keyword(s):  
Immune Cell ◽  
Cell Types ◽  
Type I ◽  
Type I Ifn ◽  
Cell Type ◽  
Gene Ablation ◽  
Cell Type Specific

IFN regulatory factor 3 (IRF3) is a transcription regulator of cellular responses in many cell types that is known to be essential for innate immunity. To confirm IRF3’s broad role in immunity and to more fully discern its role in various cellular subsets, we engineered Irf3-floxed mice to allow for the cell type-specific ablation of Irf3. Analysis of these mice confirmed the general requirement of IRF3 for the evocation of type I IFN responses in vitro and in vivo. Furthermore, immune cell ontogeny and frequencies of immune cell types were unaffected when Irf3 was selectively inactivated in either T cells or B cells in the mice. Interestingly, in a model of lipopolysaccharide-induced septic shock, selective Irf3 deficiency in myeloid cells led to reduced levels of type I IFN in the sera and increased survival of these mice, indicating the myeloid-specific, pathogenic role of the Toll-like receptor 4–IRF3 type I IFN axis in this model of sepsis. Thus, Irf3-floxed mice can serve as useful tool for further exploring the cell type-specific functions of this transcription factor.

scholarly journals Cell-Type Specific Oxytocin Gene Expression from AAV Delivered Promoter Deletion Constructs into the Rat Supraoptic Nucleus in vivo

PLoS ONE ◽  
2012 ◽  
Vol 7 (2) ◽  
pp. e32085 ◽  
Author(s):  
Raymond L. Fields ◽  
Todd A. Ponzio ◽  
Makoto Kawasaki ◽  
Harold Gainer
Keyword(s):  
Gene Expression ◽  
Supraoptic Nucleus ◽  
Cell Type ◽  
Promoter Deletion ◽  
Cell Type Specific

scholarly journals Polycomb complexes in normal and malignant hematopoiesis

2018 ◽  
Vol 218 (1) ◽  
pp. 55-69 ◽  
Author(s):  
Valerio Di Carlo ◽  
Ivano Mocavini ◽  
Luciano Di Croce
Keyword(s):  
Gene Expression ◽  
Polycomb Group ◽  
Epigenetic Mechanisms ◽  
Hematopoietic Differentiation ◽  
Cell Type ◽  
Negative Regulators ◽  
Self Renewal ◽  
Hematological Diseases ◽  
Cell Type Specific

Epigenetic mechanisms are crucial for sustaining cell type–specific transcription programs. Among the distinct factors, Polycomb group (PcG) proteins are major negative regulators of gene expression in mammals. These proteins play key roles in regulating the proliferation, self-renewal, and differentiation of stem cells. During hematopoietic differentiation, many PcG proteins are fundamental for proper lineage commitment, as highlighted by the fact that a lack of distinct PcG proteins results in embryonic lethality accompanied by differentiation biases. Correspondingly, proteins of these complexes are frequently dysregulated in hematological diseases. In this review, we present an overview of the role of PcG proteins in normal and malignant hematopoiesis, focusing on the compositional complexity of PcG complexes, and we briefly discuss the ongoing clinical trials for drugs targeting these factors.

scholarly journals Monitoring Cell-Type–Specific Gene Expression Using Ribosome Profiling In Vivo During Cardiac Hemodynamic Stress

2019 ◽  
Vol 125 (4) ◽  
pp. 431-448 ◽  
Author(s):  
Shirin Doroudgar ◽  
Christoph Hofmann ◽  
Etienne Boileau ◽  
Brandon Malone ◽  
Eva Riechert ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ribosome Profiling ◽  
Specific Gene ◽  
Cell Type ◽  
Specific Gene Expression ◽  
Hemodynamic Stress ◽  
Cell Type Specific

scholarly journals A human cell atlas of fetal chromatin accessibility

Science ◽  
2020 ◽  
Vol 370 (6518) ◽  
pp. eaba7612 ◽  
Author(s):  
Silvia Domcke ◽  
Andrew J. Hill ◽  
Riza M. Daza ◽  
Junyue Cao ◽  
Diana R. O’Day ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Cell ◽  
Single Cells ◽  
Complex Trait ◽  
Cell Types ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Cell Type ◽  
Cell Type Specific

The chromatin landscape underlying the specification of human cell types is of fundamental interest. We generated human cell atlases of chromatin accessibility and gene expression in fetal tissues. For chromatin accessibility, we devised a three-level combinatorial indexing assay and applied it to 53 samples representing 15 organs, profiling ~800,000 single cells. We leveraged cell types defined by gene expression to annotate these data and cataloged hundreds of thousands of candidate regulatory elements that exhibit cell type–specific chromatin accessibility. We investigated the properties of lineage-specific transcription factors (such as POU2F1 in neurons), organ-specific specializations of broadly distributed cell types (such as blood and endothelial), and cell type–specific enrichments of complex trait heritability. These data represent a rich resource for the exploration of in vivo human gene regulation in diverse tissues and cell types.

scholarly journals MAFB surrogates the glucocorticoid receptor ability to induce tolerogenesis in dendritic cells

2021 ◽  
Author(s):  
Octavio Morante-Palacios ◽  
Laura Ciudad ◽  
Raphael Micheroli ◽  
Carlos de la Calle-Fabregat ◽  
Tianlu Li ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Glucocorticoid Receptor ◽  
Inflammatory Diseases ◽  
Dna Demethylation ◽  
Regulatory Mechanisms ◽  
Cell Type ◽  
Cell Type Specific

Glucocorticoids (GCs) exert potent anti-inflammatory effects in immune cells through the glucocorticoid receptor (GR). Dendritic cells (DCs), central actors for coordinating immune responses, acquire tolerogenic properties in response to GCs. Tolerogenic DCs (tolDCs) have emerged as a potential treatment for various inflammatory diseases. To date, the underlying cell type-specific regulatory mechanisms orchestrating GC-mediated acquisition of immunosuppressive properties remain poorly understood. In this study, we investigated the transcriptomic and epigenomic remodeling associated with differentiation to DCs in the presence of GCs. Our analysis demonstrates a major role of MAFB in this process, in synergy with GR. GR and MAFB both interact with methylcytosine dioxygenase TET2 and bind to genomic loci that undergo specific demethylation in tolDCs. We also show that the role of MAFB is more extensive, binding to thousands of genomic loci in tolDCs. Finally, MAFB knockdown erases the tolerogenic properties of tolDCs and reverts the specific DNA demethylation and gene upregulation. The preeminent role of MAFB is also demonstrated in vivo for myeloid cells from synovium in rheumatoid arthritis following GC treatment. Our results imply that, once directly activated by GR, MAFB takes over the main roles to orchestrate the epigenomic and transcriptomic remodeling that define the tolerogenic phenotype.

scholarly journals Cell type specific gene expression profiling reveals a role for the complement component C3A in neutrophil migration to tissue damage

2019 ◽  
Author(s):  
Ruth A. Houseright ◽  
Emily E. Rosowski ◽  
Pui Ying Lam ◽  
Sebastien JM Tauzin ◽  
Oscar Mulvaney ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bacterial Infections ◽  
Large Scale ◽  
Affinity Purification ◽  
Neutrophil Migration ◽  
Acute Injury ◽  
Specific Gene ◽  
Cell Type ◽  
Cell Type Specific

AbstractFollowing acute injury, leukocytes rapidly infiltrate into tissues. For efficient recruitment, leukocytes must sense and respond to signals from both from the damaged tissue and from one another. However, the cell type specific transcriptional changes that influence leukocyte recruitment and wound healing have not been well characterized. In this study, we performed a large-scale translating ribosome affinity purification (TRAP) and RNA sequencing screen in larval zebrafish to identify genes differentially expressed by neutrophils, macrophages, and epithelial cells in the context of wounding. We identified the complement pathway and c3a.1, homologous to the C3A component of human complement, as significantly increased in neutrophils in response to a wound. We report that c3a.1−/− zebrafish larvae have impaired neutrophil responses to both tail wounds and localized bacterial infections, as well as increased susceptibility to infection due to a neutrophil-intrinsic function of C3A. We further show that C3A enhances migration of human primary neutrophils to IL-8 and that c3a.1−/− larvae have impaired neutrophil migration in vivo, and a decrease in neutrophil directed migration speed early after wounding. Together, our findings suggest a role for C3A in mediating efficient neutrophil migration to damaged tissues and support the power of TRAP to identify cell-specific changes in gene expression associated with wound-associated inflammation.

scholarly journals Mechanochemical modelling of dorsal closure reveals emergent cell behaviour in tissue morphogenesis

2020 ◽  
Author(s):  
Francesco Atzeni ◽  
Laurynas Pasakarnis ◽  
Gabriella Mosca ◽  
Richard S. Smith ◽  
Christof M. Aegerter ◽  
...  
Keyword(s):  
Dorsal Closure ◽  
Cell Type ◽  
Tissue Morphogenesis ◽  
Cell Behaviour ◽  
Actomyosin Contractility ◽  
Cell Type Specific ◽  
Mutant Phenotypes ◽  
Modelling Approach

AbstractTissue morphogenesis integrates cell type-specific biochemistry and architecture, cellular force generation and mechanisms coordinating forces amongst neighbouring cells and tissues. We use finite element-based modelling to explore the interconnections at these multiple biological scales in embryonic dorsal closure, where pulsed actomyosin contractility in adjacent Amnioserosa (AS) cells powers the closure of an epidermis opening. Based on our in vivo observations, the model implements F-actin nucleation periodicity that is independent of MyoII activity. Our model reveals conditions, where depleting MyoII activity nevertheless indirectly affects oscillatory F-actin behaviour, without the need for biochemical feedback. In addition, it questions the previously proposed role of Dpp-mediated regulation of the patterned actomyosin dynamics in the AS tissue, suggesting them to be emergent. Tissue-specific Dpp interference supports the model’s prediction. The model further predicts that the mechanical properties of the surrounding epidermis tissue feed back on the shaping and patterning of the AS tissue. Finally, our model’s parameter space reproduces mutant phenotypes and provides predictions for their underlying cause. Our modelling approach thus reveals several unappreciated mechanistic properties of tissue morphogenesis.

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