Combinatorial control of cell differentiation by cAMP and DIF-1 during development of Dictyostelium discoideum

Development ◽  
1990 ◽  
Vol 110 (3) ◽  
pp. 977-984 ◽  
Author(s):  
M. Berks ◽  
R.R. Kay
Keyword(s):  
Cell Differentiation ◽  
Normal Development ◽  
Specific Effect ◽  
Cell Types ◽  
Signal Molecules ◽  
Stage Of Development ◽  
Combinatorial Control ◽  
Cell Type Specific ◽  
Significant Pathway ◽  
Mrna Markers

At least three distinct types of cell arise from a population of similar amoebae during Dictyostelium development: prespore, prestalk A and prestalk B cells. We report evidence suggesting that this cellular diversification can be brought about by the combinatorial action of two diffusible signals, cAMP and DIF-1. Cells at different stages of normal development were transferred to shaken suspension, challenged with various combinations of signal molecules and the expression of cell-type-specific mRNA markers measured 1–2 h later. pDd63, pDd56 and D19 mRNAs were used for prestalk A, prestalk B and prespore cells respectively. We find the following results. (1) Cells first become responsive to DIF-1 for prestalk A differentiation and to cAMP for prespore differentiation at the end of aggregation, about 2 h before these cell types normally appear. (2) At the first finger stage of development, when the rate of accumulation of the markers is maximal, the expression of each is favoured by a unique combination of effectors: prespore differentiation is stimulated by cAMP and inhibited by DIF-1; prestalk A differentiation is stimulated by both cAMP and DIF-1 and prestalk B differentiation is stimulated by DIF-1 and inhibited by cAMP. (3) Half-maximal effects are produced by 10–70 nM DIF-1, which is in the physiological range. (4) Ammonia and adenosine, which can affect cell differentiation in other circumstances, have no significant pathway-specific effect in our conditions. These results suggest that cell differentiation could be brought about in normal development by the localized action of cAMP and DIF-1.

scholarly journals Analysis of putative cis-regulatory elements regulating blood pressure variation

2020 ◽  
Vol 29 (11) ◽  
pp. 1922-1932
Author(s):  
Priyanka Nandakumar ◽  
Dongwon Lee ◽  
Thomas J Hoffmann ◽  
Georg B Ehret ◽  
Dan Arking ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Association Studies ◽  
Specific Effect ◽  
Cell Types ◽  
Regulatory Elements ◽  
Open Chromatin ◽  
Genome Wide Association Studies ◽  
Cell Type ◽  
Functional Scores ◽  
Cell Type Specific

Abstract Hundreds of loci have been associated with blood pressure (BP) traits from many genome-wide association studies. We identified an enrichment of these loci in aorta and tibial artery expression quantitative trait loci in our previous work in ~100 000 Genetic Epidemiology Research on Aging study participants. In the present study, we sought to fine-map known loci and identify novel genes by determining putative regulatory regions for these and other tissues relevant to BP. We constructed maps of putative cis-regulatory elements (CREs) using publicly available open chromatin data for the heart, aorta and tibial arteries, and multiple kidney cell types. Variants within these regions may be evaluated quantitatively for their tissue- or cell-type-specific regulatory impact using deltaSVM functional scores, as described in our previous work. We aggregate variants within these putative CREs within 50 Kb of the start or end of ‘expressed’ genes in these tissues or cell types using public expression data and use deltaSVM scores as weights in the group-wise sequence kernel association test to identify candidates. We test for association with both BP traits and expression within these tissues or cell types of interest and identify the candidates MTHFR, C10orf32, CSK, NOV, ULK4, SDCCAG8, SCAMP5, RPP25, HDGFRP3, VPS37B and PPCDC. Additionally, we examined two known QT interval genes, SCN5A and NOS1AP, in the Atherosclerosis Risk in Communities Study, as a positive control, and observed the expected heart-specific effect. Thus, our method identifies variants and genes for further functional testing using tissue- or cell-type-specific putative regulatory information.

scholarly journals Single Cell Transcriptomics Reveals Dysregulated Cellular and Molecular Networks in a Fragile X Syndrome model

2020 ◽  
Author(s):  
Elisa Donnard ◽  
Huan Shu ◽  
Manuel Garber
Keyword(s):  
Single Cell ◽  
Fragile X Syndrome ◽  
Fragile X ◽  
Expression Profiles ◽  
Specific Effect ◽  
Cell Types ◽  
Tissue Expression ◽  
Molecular Networks ◽  
Cell Type ◽  
Cell Type Specific

AbstractDespite advances in understanding the pathophysiology of Fragile X syndrome (FXS), its molecular bases are still poorly understood. Whole brain tissue expression profiles have proved surprisingly uninformative. We applied single cell RNA sequencing to profile a FXS mouse model. We found that FXS results in a highly cell type specific effect and it is strongest among different neuronal types. We detected a downregulation of mRNAs bound by FMRP and this effect is prominent in neurons. Metabolic pathways including translation are significantly upregulated across all cell types with the notable exception of excitatory neurons. These effects point to a potential difference in the activity of mTOR pathways, and together with other dysregulated pathways suggest an excitatory-inhibitory imbalance in the FXS cortex which is exacerbated by astrocytes. Our data demonstrate the cell-type specific complexity of FXS and provide a resource for interrogating the biological basis of this disorder.

Cellular heterogeneity of human fallopian tubes in normal and hydrosalpinx disease states identified by scRNA-seq

2021 ◽  
Author(s):  
Nicole D Ulrich ◽  
Yu-chi Shen ◽  
Qianyi Ma ◽  
Kun Yang ◽  
D Ford Hannum ◽  
...  
Keyword(s):  
Fallopian Tube ◽  
Normal Development ◽  
Cell Types ◽  
Cellular Heterogeneity ◽  
Secretory Cells ◽  
Fallopian Tubes ◽  
Dynamic Regulation ◽  
Future Studies ◽  
Disease States ◽  
Cell Type Specific

Fallopian tube (FT) homeostasis requires dynamic regulation of heterogeneous cell populations and is disrupted in infertility and ovarian cancer. Here we applied single-cell RNAseq to profile 53,376 FT cells from 3 healthy pre-menopausal subjects. The resulting cell atlas contains 12 major cell types representing epithelial, stromal and immune compartments. Re-clustering of epithelial cells identified 4 ciliated and 6 non-ciliated secretory epithelial subtypes, two of which represent potential progenitor pools: one leading to mature secretory cells, while the other contributing to either ciliated cells or one of the stromal cell types. To understand how FT cell numbers and states change in a disease state, we analyzed ~15,000 cells from a hydrosalpinx sample and observed shifts in epithelial and stromal populations, and cell type-specific changes in extracellular matrix and TGF-β signaling, underscoring fibrosis pathophysiology. This resource is expected to facilitate future studies to understand fallopian tube homeostasis in normal development and disease.

Organization and cell differentiation in lateral roots of Arabidopsis thaliana

Development ◽  
1997 ◽  
Vol 124 (1) ◽  
pp. 33-44 ◽  
Author(s):  
J.E. Malamy ◽  
P.N. Benfey
Keyword(s):  
Arabidopsis Thaliana ◽  
Cell Differentiation ◽  
Lateral Root ◽  
Lateral Roots ◽  
Cell Types ◽  
Cell Type ◽  
Root Primordia ◽  
Lateral Root Primordia ◽  
Lateral Root Development ◽  
Cell Type Specific

Lateral root formation in plants involves the stimulation of mature pericycle cells to proliferate and redifferentiate to create a new organ. The simple organization of the root of Arabidopsis thaliana allows the development of lateral root primordia to be characterized histologically. We have divided the process of lateral root development into 8 stages defined by specific anatomical characteristics and cell divisions. To identify the cell types in the developing primordium we have generated a collection of marker lines that express beta-glucuronidase in a tissue- or cell type-specific manner in the root. Using these tools we have constructed a model describing the lineage of each cell type in the lateral root. These studies show that organization and cell differentiation in the lateral root primordia precede the appearance of a lateral root meristem, with differential gene expression apparent after the first set of divisions of the pericycle.

Neuronal mRNA Translation in Addiction

2018 ◽  
Author(s):  
Emma Puighermanal ◽  
Emmanuel Valjent
Keyword(s):  
Structural Changes ◽  
Drugs Of Abuse ◽  
Mrna Translation ◽  
Cell Types ◽  
Behavioral Changes ◽  
Translational Machinery ◽  
Addictive Drugs ◽  
Specific Mrnas ◽  
Cell Type Specific ◽  
Future Work

Addictive drugs trigger persistent synaptic and structural changes in the neuronal reward circuits that are thought to underlie the development of drug-adaptive behavior. While transcriptional and epigenetic modifications are known to contribute to these circuit changes, accumulating evidence indicates that altered mRNA translation is also a key molecular mechanism. This chapter reviews recent studies demonstrating how addictive drugs alter protein synthesis and/or the translational machinery and how this leads to neuronal circuit remodeling and behavioral changes. Future work will determine precisely which neuronal circuits and cell types participate in these changes. The chapter summarizes current methodologies for identifying cell type-specific mRNAs whose translation is affected by drugs of abuse and gives recent examples of the mechanistic insights into addiction they provide.

scholarly journals scSorter: assigning cells to known cell types according to marker genes

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Hongyu Guo ◽  
Jun Li
Keyword(s):  
Real Data ◽  
Cell Types ◽  
Exact Expression ◽  
Marker Genes ◽  
Specific Marker ◽  
Sequencing Data ◽  
Reference Dataset ◽  
Over Expression ◽  
Higher Power ◽  
Cell Type Specific

AbstractOn single-cell RNA-sequencing data, we consider the problem of assigning cells to known cell types, assuming that the identities of cell-type-specific marker genes are given but their exact expression levels are unavailable, that is, without using a reference dataset. Based on an observation that the expected over-expression of marker genes is often absent in a nonnegligible proportion of cells, we develop a method called scSorter. scSorter allows marker genes to express at a low level and borrows information from the expression of non-marker genes. On both simulated and real data, scSorter shows much higher power compared to existing methods.

scholarly journals Interplay of BAF and MLL4 promotes cell type-specific enhancer activation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Young-Kwon Park ◽  
Ji-Eun Lee ◽  
Zhijiang Yan ◽  
Kaitlin McKernan ◽  
Tommy O’Haren ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Chromatin Remodeling ◽  
Direct Evidence ◽  
Cell Type ◽  
Chromatin Regulators ◽  
Chromatin Remodeling Complex ◽  
Histone H3k4 ◽  
Cell Type Specific ◽  
Pioneer Transcription Factor ◽  
Factor C

AbstractCell type-specific enhancers are activated by coordinated actions of lineage-determining transcription factors (LDTFs) and chromatin regulators. The SWI/SNF chromatin remodeling complex BAF and the histone H3K4 methyltransferase MLL4 (KMT2D) are both implicated in enhancer activation. However, the interplay between BAF and MLL4 in enhancer activation remains unclear. Using adipogenesis as a model system, we identify BAF as the major SWI/SNF complex that colocalizes with MLL4 and LDTFs on active enhancers and is required for cell differentiation. In contrast, the promoter enriched SWI/SNF complex PBAF is dispensable for adipogenesis. By depleting BAF subunits SMARCA4 (BRG1) and SMARCB1 (SNF5) as well as MLL4 in cells, we show that BAF and MLL4 reciprocally regulate each other’s binding on active enhancers before and during adipogenesis. By focusing on enhancer activation by the adipogenic pioneer transcription factor C/EBPβ without inducing cell differentiation, we provide direct evidence for an interdependent relationship between BAF and MLL4 in activating cell type-specific enhancers. Together, these findings reveal a positive feedback between BAF and MLL4 in promoting LDTF-dependent activation of cell type-specific enhancers.

scholarly journals Connectivity characterization of the mouse basolateral amygdalar complex

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Houri Hintiryan ◽  
Ian Bowman ◽  
David L. Johnson ◽  
Laura Korobkova ◽  
Muye Zhu ◽  
...  
Keyword(s):  
Granular Cell ◽  
Cell Types ◽  
Projection Neurons ◽  
Cell Type ◽  
Connectivity Map ◽  
Analysis Techniques ◽  
Domain Specific ◽  
Cell Type Specific ◽  
Unique Domain

AbstractThe basolateral amygdalar complex (BLA) is implicated in behaviors ranging from fear acquisition to addiction. Optogenetic methods have enabled the association of circuit-specific functions to uniquely connected BLA cell types. Thus, a systematic and detailed connectivity profile of BLA projection neurons to inform granular, cell type-specific interrogations is warranted. Here, we apply machine-learning based computational and informatics analysis techniques to the results of circuit-tracing experiments to create a foundational, comprehensive BLA connectivity map. The analyses identify three distinct domains within the anterior BLA (BLAa) that house target-specific projection neurons with distinguishable morphological features. We identify brain-wide targets of projection neurons in the three BLAa domains, as well as in the posterior BLA, ventral BLA, posterior basomedial, and lateral amygdalar nuclei. Inputs to each nucleus also are identified via retrograde tracing. The data suggests that connectionally unique, domain-specific BLAa neurons are associated with distinct behavior networks.

scholarly journals Shisa6 mediates cell-type specific regulation of depression in the nucleus accumbens

2021 ◽  
Author(s):  
Hee-Dae Kim ◽  
Jing Wei ◽  
Tanessa Call ◽  
Nicole Teru Quintus ◽  
Alexander J. Summers ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Current Treatment ◽  
Specific Cell ◽  
Excitatory Synapses ◽  
Cell Type ◽  
Cell Type Specific ◽  
Specific Regulation ◽  
Circuit Function

AbstractDepression is the leading cause of disability and produces enormous health and economic burdens. Current treatment approaches for depression are largely ineffective and leave more than 50% of patients symptomatic, mainly because of non-selective and broad action of antidepressants. Thus, there is an urgent need to design and develop novel therapeutics to treat depression. Given the heterogeneity and complexity of the brain, identification of molecular mechanisms within specific cell-types responsible for producing depression-like behaviors will advance development of therapies. In the reward circuitry, the nucleus accumbens (NAc) is a key brain region of depression pathophysiology, possibly based on differential activity of D1- or D2- medium spiny neurons (MSNs). Here we report a circuit- and cell-type specific molecular target for depression, Shisa6, recently defined as an AMPAR component, which is increased only in D1-MSNs in the NAc of susceptible mice. Using the Ribotag approach, we dissected the transcriptional profile of D1- and D2-MSNs by RNA sequencing following a mouse model of depression, chronic social defeat stress (CSDS). Bioinformatic analyses identified cell-type specific genes that may contribute to the pathogenesis of depression, including Shisa6. We found selective optogenetic activation of the ventral tegmental area (VTA) to NAc circuit increases Shisa6 expression in D1-MSNs. Shisa6 is specifically located in excitatory synapses of D1-MSNs and increases excitability of neurons, which promotes anxiety- and depression-like behaviors in mice. Cell-type and circuit-specific action of Shisa6, which directly modulates excitatory synapses that convey aversive information, identifies the protein as a potential rapid-antidepressant target for aberrant circuit function in depression.

scholarly journals Histone modifications form a cell-type-specific chromosomal bar code that persists through the cell cycle

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
John A. Halsall ◽  
Simon Andrews ◽  
Felix Krueger ◽  
Charlotte E. Rutledge ◽  
Gabriella Ficz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Histone Modifications ◽  
Expression Patterns ◽  
Cell Types ◽  
Cell Type ◽  
Bar Code ◽  
Genes Encoding ◽  
Cell Type Specific ◽  
Rolling Windows

AbstractChromatin configuration influences gene expression in eukaryotes at multiple levels, from individual nucleosomes to chromatin domains several Mb long. Post-translational modifications (PTM) of core histones seem to be involved in chromatin structural transitions, but how remains unclear. To explore this, we used ChIP-seq and two cell types, HeLa and lymphoblastoid (LCL), to define how changes in chromatin packaging through the cell cycle influence the distributions of three transcription-associated histone modifications, H3K9ac, H3K4me3 and H3K27me3. We show that chromosome regions (bands) of 10–50 Mb, detectable by immunofluorescence microscopy of metaphase (M) chromosomes, are also present in G1 and G2. They comprise 1–5 Mb sub-bands that differ between HeLa and LCL but remain consistent through the cell cycle. The same sub-bands are defined by H3K9ac and H3K4me3, while H3K27me3 spreads more widely. We found little change between cell cycle phases, whether compared by 5 Kb rolling windows or when analysis was restricted to functional elements such as transcription start sites and topologically associating domains. Only a small number of genes showed cell-cycle related changes: at genes encoding proteins involved in mitosis, H3K9 became highly acetylated in G2M, possibly because of ongoing transcription. In conclusion, modified histone isoforms H3K9ac, H3K4me3 and H3K27me3 exhibit a characteristic genomic distribution at resolutions of 1 Mb and below that differs between HeLa and lymphoblastoid cells but remains remarkably consistent through the cell cycle. We suggest that this cell-type-specific chromosomal bar-code is part of a homeostatic mechanism by which cells retain their characteristic gene expression patterns, and hence their identity, through multiple mitoses.

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