scholarly journals Regulation of spatial and temporal gene expression in an animal germline

2018 ◽  
Author(s):  
Asija Diag ◽  
Marcel Schilling ◽  
Filippos Klironomos ◽  
Salah Ayoub ◽  
Nikolaus Rajewsky
Keyword(s):  
Gene Expression ◽  
Regulatory Mechanisms ◽  
Rna Expression ◽  
Temporal Expression ◽  
Temporal Gene Expression ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Gene Regulatory ◽  
Spatio Temporal

SUMMARYIn animal germlines, regulation of cell proliferation and differentiation is particularly important but poorly understood. Here, using a cryo-cut approach, we mapped RNA expression along the Caenorhabditis elegans germline and, using mutants, dissected gene regulatory mechanisms that control spatio-temporal expression. We detected, at near single-cell resolution, > 10,000 mRNAs, > 300 miRNAs and numerous novel miRNAs. Most RNAs were organized in distinct spatial patterns. Germline-specific miRNAs and their targets were co-localized. Moreover, we observed differential 3’ UTR isoform usage for hundreds of mRNAs. In tumorous gld-2 gld-1 mutants, gene expression was strongly perturbed. In particular, differential 3’ UTR usage was significantly impaired. We propose that PIE-1, a transcriptional repressor, functions to maintain spatial gene expression. Our data also suggest that cpsf-4 and fipp-1 control differential 3’ UTR usage for hundreds of genes. Finally, we constructed a “virtual gonad” enabling “virtual in situ hybridizations” and access to all data (https://shiny.mdc-berlin.de/spacegerm/).

scholarly journals Gene expression underlying floral epidermal specialization inAristolochia fimbriata(Aristolochiaceae)

2021 ◽  
Author(s):  
Harold Suárez-Baron ◽  
Juan F Alzate ◽  
Favio González ◽  
Soraya Pelaz ◽  
Barbara A Ambrose ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Genetic Network ◽  
Small Subset ◽  
Temporal Expression ◽  
Trichome Development ◽  
Spatio Temporal

AbstractBackground and AimsThe epidermis constitutes the outermost tissue of the plant body. Although it plays major structural, physiological and ecological roles in embryophytes, the molecular mechanisms controlling epidermal cell fate, differentiation and trichome development have been scarcely studied across angiosperms, and remain almost unexplored in floral organs.MethodsIn this study, we assess the spatio-temporal expression patterns of GL2, GL3, TTG1, TRY, MYB5, MYB6, HDG2, MYB106-like, WIN1 and RAV1-like homologues in the magnoliid Aristolochia fimbriata (Aristolochiaceae) by using comparative RNA-sequencing and in situ hybridization assays.Key ResultsGenes involved in Aristolochia fimbriata trichome development vary depending on the organ where they are formed. Stem, leaf and pedicel trichomes recruit most of the transcription factors (TFs) described above. Conversely, floral trichomes only use a small subset of genes including AfimGL2, AfimRAV1-like, AfimWIN1, AfimMYB106-like and AfimHDG2. The remaining TFs, AfimTTG1, AfimGL3, AfimTRY, AfimMYB5 and AfimMYB6, are restricted to the abaxial (outer) and the adaxial (inner) pavement epidermal cells.ConclusionsWe re-evaluate the core genetic network shaping trichome fate in flowers of an early-divergent angiosperm lineage and show a morphologically diverse output with a simpler genetic mechanism in place when compared to the models Arabidopsis thaliana and Cucumis sativus. In turn, our results strongly suggest that the canonical trichome gene expression appears to be more conserved in vegetative than in floral tissues across angiosperms.

Contrasting patterns of c-myc and N-myc expression in proliferating, quiescent, and differentiating cells of the embryonic chicken lens

Development ◽  
1992 ◽  
Vol 115 (3) ◽  
pp. 813-820
Author(s):  
L.L. Harris ◽  
J.C. Talian ◽  
P.S. Zelenka
Keyword(s):  
Cell Proliferation ◽  
Protein Product ◽  
Mrna Levels ◽  
Lens Fiber ◽  
Proliferating Cells ◽  
Fiber Cells ◽  
Embryonic Chicken ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation

The present study uses the polymerase chain reaction and in situ hybridization to examine c-myc and N-myc mRNA in the embryonic chicken lens at 6, 10, 14 and 19 days of development and compares the pattern of expression obtained with the developmental pattern of cell proliferation and differentiation. In the central epithelium, c-myc mRNA levels were proportional to the percentage of proliferating cells throughout development. N-myc mRNA expression in this region was relatively low and showed no correlation with cell proliferation. The ratio of N-myc to c-myc mRNA increased markedly with the onset of epithelial cell elongation and terminal fiber cell differentiation, although both c-myc and N-myc mRNAs continued to be expressed in postmitotic, elongating cells of the equatorial epithelium and in terminally differentiating lens fiber cells. Thus, increased expression of N-myc, a gene whose protein product may compete with c-myc protein for dimerization partners, accompanies the dissociation of c-myc expression and cell proliferation during terminal differentiation of lens fiber cells.

scholarly journals Mamo decodes hierarchical temporal gradients into terminal neuronal fate

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Ling-Yu Liu ◽  
Xi Long ◽  
Ching-Po Yang ◽  
Rosa L Miyares ◽  
Ken Sugino ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Neuronal Diversity ◽  
Temporal Expression ◽  
Identity Maintenance ◽  
Temporal Gene Expression ◽  
Neuronal Fate ◽  
Mammalian Genes ◽  
Post Transcriptional Regulation

Temporal patterning is a seminal method of expanding neuronal diversity. Here we unravel a mechanism decoding neural stem cell temporal gene expression and transforming it into discrete neuronal fates. This mechanism is characterized by hierarchical gene expression. First, Drosophila neuroblasts express opposing temporal gradients of RNA-binding proteins, Imp and Syp. These proteins promote or inhibit chinmo translation, yielding a descending neuronal gradient. Together, first and second-layer temporal factors define a temporal expression window of BTB-zinc finger nuclear protein, Mamo. The precise temporal induction of Mamo is achieved via both transcriptional and post-transcriptional regulation. Finally, Mamo is essential for the temporally defined, terminal identity of α’/β’ mushroom body neurons and identity maintenance. We describe a straightforward paradigm of temporal fate specification where diverse neuronal fates are defined via integrating multiple layers of gene regulation. The neurodevelopmental roles of orthologous/related mammalian genes suggest a fundamental conservation of this mechanism in brain development.

scholarly journals The influence of direct and indirect fibroblast cell contact on human myogenic cell behavior and gene expression in vitro

2019 ◽  
Vol 127 (2) ◽  
pp. 342-355 ◽  
Author(s):  
Cecilie J. L. Bechshøft ◽  
Peter Schjerling ◽  
Michael Kjaer ◽  
Abigail L. Mackey
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Cell Proliferation ◽  
Myogenic Cell ◽  
Mrna Levels ◽  
Indirect Contact ◽  
Permeable Membrane ◽  
Primary Myoblasts ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation

Underpinning skeletal muscle plasticity is the interplay between many cell types, of which fibroblasts are emerging as potent players, both negatively in the development of fibrosis but also positively in stimulating muscle repair through enhancing myogenesis. The mechanisms behind this interaction however remain unknown. To investigate this, waste hamstring muscle tissue was obtained from eight healthy young men undergoing reconstructive anterior cruciate ligament surgery and primary myoblasts and fibroblasts were isolated. Myoblasts were cultured alone or with fibroblasts, either in direct or indirect contact (separated by an insert with a permeable membrane). The myogenesis parameters proliferation, differentiation, and fusion were determined from immunostained cells, while, in replicate samples, gene expression levels of GAPDH, Ki67, Pax7, MyoD, myogenin, myomaker, MHC-Iβ, TCF7L2, COL1A1, and p16 were determined by RT-PCR. We found only trends for an influence of skeletal muscle fibroblasts on myogenic cell proliferation and differentiation. While greater mRNA levels of GAPDH, Pax7, MyoD, myogenin, and MHC-Iβ were observed in myogenic cells in indirect contact with fibroblasts (insert) when compared with cells cultured alone, a similar effect of an empty insert was also observed. In conclusion we find very little influence of skeletal muscle fibroblasts on myoblasts derived from the same tissue, although it cannot be excluded that a different outcome would be seen under less optimal myogenic growth conditions. NEW & NOTEWORTHY Using passage one primary myoblasts and fibroblasts isolated from human skeletal muscle, we found only a trend for an effect of skeletal muscle fibroblasts on myogenic cell proliferation and differentiation. This is contrary to previous reports and raises the possibility that fibroblasts of different tissue origins exert distinct roles.

scholarly journals Gene Regulatory Mechanisms Underlying the Spatial and Temporal Regulation of Target-Dependent Gene Expression in Drosophila Neurons

PLoS Genetics ◽  
2015 ◽  
Vol 11 (12) ◽  
pp. e1005754 ◽  
Author(s):  
Anthony J. E. Berndt ◽  
Jonathan C. Y. Tang ◽  
Marc S. Ridyard ◽  
Tianshun Lian ◽  
Kathleen Keatings ◽  
...  
Keyword(s):  
Gene Expression ◽  
Regulatory Mechanisms ◽  
Temporal Regulation ◽  
Gene Regulatory

scholarly journals Dysregulation of ANKRD11 Influenced Hematopoisis By Histone Acetylation-Mediated Gene Expression in Myelodysplastic Syndrome

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4292-4292
Author(s):  
Youshan Zhao ◽  
Feng Xu ◽  
Juan Guo ◽  
Sida Zhao ◽  
Chunkang Chang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Histone Acetylation ◽  
Mrna Expression ◽  
Cell Line ◽  
Expression Levels ◽  
Target Sequencing ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Mrna Expression Levels

Abstract Background and Object In addition to histone deacetylation, the importance of histone over-acetylation induced oncogene transcription in initiation and progression of myelodysplastic syndrome (MDS) has been proposed recently. Our previous whole-exome sequencing identified a new somatic mutation, ANKRD11, an important factor in histone acetylation regulation. Its roles in MDS pathophysiology need to be clarified. Methods The next generation target sequencing (Including ANKRD11) was carried out in 320 patients with MDS using the MiSeq Benchtop Sequencer. ANKRD11 mRNA expression in bone marrow of MDS was measured by real-time PCR. Loss and gain of function assay were carried out in myeloid cell lines K562, MEG-01£¬or SKM-1 to observe the influence on cell proliferation and differentiation . The levels of histone acetylation at H3 and H4 were detected by Western blot. Results Target sequencing in a cohort of 320 MDS patients identified 14 of ANKRD11 mutations (4.38%, Fig.1), which were confirmed by Sanger sequencing. Meanwhile, no ANKRD11 mutations in 100 normal controls were defined. ANKRD11 mutations occurred frequently in exons 10 and 9. The mRNA expression levels of ANKRD11 were significantly decreased in MDS patients, especially in ANKRD11mutant patients (Fig.2). ANKRD11 knockdown in K562 and MEG-1 resulted in growth inhibition, cell cycle arrest and erythroid/megakaryocytic differentiation retardant. In MDS cell line SKM-1, the arrested differentiation was rescued by over-expression of ANKRD11. Consistent with a role for ANKRD11 in histone acetylation, ANKRD11 KD increased acetylation of histones H3 and H4 at H3K14 and H4K5 and resulted in the upregulation of genes involved in differentiation inhibilation (SOX6, P21, et al). Finally, the ANKRD11 KD-mediated influence on cell proliferation and differentiation were reversed by inhibiting histone acetyltransferase activity. Conclusion Our assay defined that ANKRD11 was a crucial chromatin regulator that suppress histone acetylation and then decrease gene expression during myeloid differentiation, providing a likely explanation for its role in MDS pathogenesis. This study further support histone acetylase inhibitor as a potential treatment in MDS. Figure ANKRD11mutation distribution (a) and coexist with other mutations (b). Figure. ANKRD11mutation distribution (a) and coexist with other mutations (b). Figure The mRNA expression levels of ANKRD11in our MDS (A, C) subset and GEO data (B). Figure. The mRNA expression levels of ANKRD11in our MDS (A, C) subset and GEO data (B). Changes of histone acetylation in ANKRD11-KD cell line (MEG-01). ANKRD11 KD significantly increased acetylation of histones H3 and H4 at H3K14 and H4K5. Changes of histone acetylation in ANKRD11-KD cell line (MEG-01). ANKRD11 KD significantly increased acetylation of histones H3 and H4 at H3K14 and H4K5. Disclosures No relevant conflicts of interest to declare.

scholarly journals Genome edited colorectal cancer organoid models reveal distinct microRNA activity patterns across different mutation profiles

2021 ◽  
Author(s):  
Jonathan W Villanueva ◽  
Lawrence Kwong ◽  
Teng Han ◽  
Salvador Alonso Martinez ◽  
Fong Cheng Pan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Genetically Modified ◽  
Activity Patterns ◽  
Expression Patterns ◽  
Regulatory Mechanisms ◽  
Oncogenic Mutations ◽  
Gene Regulatory ◽  
Insight Into

Somatic mutations drive colorectal cancer (CRC) by disrupting gene regulatory mechanisms. Distinct combinations of mutations can result in unique changes to regulatory mechanisms leading to variability in the efficacy of therapeutics. MicroRNAs are important regulators of gene expression, and their activity can be altered by oncogenic mutations. However, it is unknown how distinct combinations of CRC-risk mutations differentially affect microRNAs. Here, using genetically-modified mouse intestinal organoid (enteroid) models, we identify ten different modules of microRNA expression patterns across distinct combinations of mutations common in CRC. We also show that miR-24-3p, which is aberrant in genetically-modified mouse enteroids and human colonoids irrespective of mutational context, is a master regulator of gene expression in CRC. In follow-up experiments, we also demonstrate that miR-24 promotes CRC cell survival. These findings offer insight into the mechanisms that drive inter-tumor heterogeneity and highlight candidate microRNA therapeutic targets for the advancement of precision medicine for CRC.

Sign in / Sign up

Export Citation Format

Share Document