Browse
Submit Data
Databases
API
Help

Dataset Information

27 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Pancreatic Ppy-expressing γ-cells display mixed phenotypic traits and the adaptive plasticity to engage insulin production.

ABSTRACT: The cellular identity of pancreatic polypeptide (Ppy)-expressing γ-cells, one of the rarest pancreatic islet cell-type, remains elusive. Within islets, glucagon and somatostatin, released respectively from α- and δ-cells, modulate the secretion of insulin by β-cells. Dysregulation of insulin production raises blood glucose levels, leading to diabetes onset. Here, we present the genetic signature of human and mouse γ-cells. Using different approaches, we identified a set of genes and pathways defining their functional identity. We found that the γ-cell population is heterogeneous, with subsets of cells producing another hormone in addition to Ppy. These bihormonal cells share identity markers typical of the other islet cell-types. In mice, Ppy gene inactivation or conditional γ-cell ablation did not alter glycemia nor body weight. Interestingly, upon β-cell injury induction, γ-cells exhibited gene expression changes and some of them engaged insulin production, like α- and δ-cells. In conclusion, we provide a comprehensive characterization of γ-cells and highlight their plasticity and therapeutic potential.

SUBMITTER: Perez-Frances M

PROVIDER: S-EPMC8298494 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Pancreatic Ppy-expressing gamma-cells display mixed phenotypic traits and adaptive plasticity to engage insulin production

Project description:The cellular identity of pancreatic polypeptide (Ppy)-expressing γ-cells, the rarest pancreatic islet cell-type, remains elusive. Within islets, glucagon and somatostatin, released respectively from α- and δ-cells, modulate the secretion of insulin by β-cells. Dysregulation of insulin production raises blood glucose levels, leading to diabetes onset. Here, we present the genetic signature of human and mouse γ-cells. Using newly developed tools, we identified a set of genes and pathways defining their functional identity. We found that the γ-cell population is heterogeneous, with subsets of cells producing another hormone in addition to Ppy. These bihormonal cells share identity markers typical of the other islet cell-types. In mice, Ppy gene inactivation or conditional γ-cell ablation did not alter glycemia nor body weight. Interestingly, upon β-cell injury induction, γ-cells exhibited gene expression changes and some of them engaged insulin production, like α- and δ-cells. In conclusion, we provide a comprehensive characterization of γ-cells and highlight their plasticity and therapeutic potential.

2021-06-04 | GSE156665 | GEO

Pancreatic Ppy-expressing gamma-cells display mixed phenotypic traits and adaptive plasticity to engage insulin production

Project description:Pancreatic Ppy-expressing gamma-cells display mixed phenotypic traits and adaptive plasticity to engage insulin production

| PRJNA658601 | ENA

Adaptive phenotypic plasticity for life-history and less fitness-related traits.

Project description:Organisms are faced with variable environments and one of the most common solutions to cope with such variability is phenotypic plasticity, a modification of the phenotype to the environment. These modifications are commonly modelled in evolutionary theories as adaptive, influencing ecological and evolutionary processes. If plasticity is adaptive, we would predict that the closer to fitness a trait is, the less plastic it would be. To test this hypothesis, we conducted a meta-analysis of 213 studies and measured the plasticity of each reported trait as a coefficient of variation. Traits were categorized as closer to fitness-life-history traits including reproduction and survival related traits, and farther from fitness-non-life-history traits including traits related to development, metabolism and physiology, morphology and behaviour. Our results showed, unexpectedly, that although traits differed in their amounts of plasticity, trait plasticity was not related to its proximity to fitness. These findings were independent of taxonomic groups or environmental types assessed. We caution against general expectations that plasticity is adaptive, as assumed by many models of its evolution. More studies are needed that test the adaptive nature of plasticity, and additional theoretical explorations on adaptive and non-adaptive plasticity are encouraged.

| S-EPMC6571476 | biostudies-literature

Adaptive phenotypic plasticity in a clonal invader.

Project description:Organisms featuring wide trait variability and occurring in a wide range of habitats, such as the ovoviviparous New Zealand freshwater snail Potamopyrgus antipodarum, are ideal models to study adaptation. Since the mid-19th century, P. antipodarum, characterized by extremely variable shell morphology, has successfully invaded aquatic areas on four continents. Because these obligately and wholly asexual invasive populations harbor low genetic diversity compared to mixed sexual/asexual populations in the native range, we hypothesized that (1) this phenotypic variation in the invasive range might be adaptive with respect to colonization of novel habitats, and (2) that at least some of the variation might be caused by phenotypic plasticity. We surveyed 425 snails from 21 localities across northwest Europe to attempt to disentangle genetic and environmental effects on shell morphology. We analyzed brood size as proxy for fitness and shell geometric morphometrics, while controlling for genetic background. Our survey revealed 10 SNP genotypes nested into two mtDNA haplotypes and indicated that mainly lineage drove variation in shell shape but not size. Physicochemical parameters affected both shell shape and size and the interaction of these traits with brood size. In particular, stronger stream flow rates were associated with larger shells. Our measurements of brood size suggested that relatively larger slender snails with relatively large apertures were better adapted to strong flow than counterparts with broader shells and relatively small apertures. In conclusion, the apparent potential to modify shell morphology plays likely a key role in the invasive success of P. antipodarum; the two main components of shell morphology, namely shape and size, being differentially controlled, the former mainly genetically and the latter predominantly by phenotypic plasticity.

| S-EPMC5938463 | biostudies-literature

Trait-specific consequences of inbreeding on adaptive phenotypic plasticity.

Project description:Environmental changes may stress organisms and stimulate an adaptive phenotypic response. Effects of inbreeding often interact with the environment and can decrease fitness of inbred individuals exposed to stress more so than that of outbred individuals. Such an interaction may stem from a reduced ability of inbred individuals to respond plastically to environmental stress; however, this hypothesis has rarely been tested. In this study, we mimicked the genetic constitution of natural inbred populations by rearing replicate Drosophila melanogaster populations for 25 generations at a reduced population size (10 individuals). The replicate inbred populations, as well as control populations reared at a population size of 500, were exposed to a benign developmental temperature and two developmental temperatures at the lower and upper margins of their viable range. Flies developed at the three temperatures were assessed for traits known to vary across temperatures, namely abdominal pigmentation, wing size, and wing shape. We found no significant difference in phenotypic plasticity in pigmentation or in wing size between inbred and control populations, but a significantly higher plasticity in wing shape across temperatures in inbred compared to control populations. Given that the norms of reaction for the noninbred control populations are adaptive, we conclude that a reduced ability to induce an adaptive phenotypic response to temperature changes is not a general consequence of inbreeding and thus not a general explanation of inbreeding-environment interaction effects on fitness components.

| S-EPMC4298428 | biostudies-literature

IL-22-Expressing Murine Lymphocytes Display Plasticity and Pathogenicity in Reporter Mice.

Project description:IL-22 has multiple activities ranging from tissue repair to inflammation. To characterize the pathogenicity and plasticity of cells that produce IL-22, a novel reporter mouse strain was generated. Homeostatic IL-22 reporter expression was observed in intestinal lymphoid cells identified as CD4 T cells and ILC3 cells. In a model of inflammatory bowel disease, CD4 T cells strongly expressed the IL-22 reporter in mesenteric lymph node. To examine plasticity of IL-22(+) T cells, they were purified after generation in vitro or in vivo from inflamed colon, and then cultured under Th1, Th2, or Th17 conditions. In vitro-generated IL-22(+) CD4 T cells showed relatively durable IL-22 expression under Th1 or Th2 conditions, whereas in vivo-generated cells rapidly lost IL-22 expression under these conditions. In vitro-generated cells could not be diverted to express Th1 or Th2 cytokines despite the expression of "master regulators." In vivo-generated cells could be diverted, at very low frequency, to express Th1 or Th2 cytokines. Both in vitro- and in vivo-generated cells could be induced in vitro to express high levels of IL-17A and IL-17F, assigning them to a "Th17 biased" class. However, IL-27 potently downregulated IL-22 expression. To examine IL-22(+) T cell pathogenicity, in vitro-generated cells were transferred into Rag1(-/-) mice, retaining the modest reporter expression and inducing moderate colitis. In contrast, IL-22 expressers from colitic mice, transferred into secondary hosts, lost reporter expression, acquired high T-bet and modest IFN? and IL-17 expression, and induced severe colitis. These findings are consistent with a model of strong polarization under optimal in vitro conditions, but a plastic state of T cells in vivo.

| S-EPMC4717188 | biostudies-literature

Phenotypic plasticity can facilitate adaptive evolution in gene regulatory circuits.

Project description:BackgroundMany important evolutionary adaptations originate in the modification of gene regulatory circuits to produce new gene activity phenotypes. How do evolving populations sift through an astronomical number of circuits to find circuits with new adaptive phenotypes? The answer may often involve phenotypic plasticity. Phenotypic plasticity allows a genotype to produce different - alternative - phenotypes after non-genetic perturbations that include gene expression noise, environmental change, or epigenetic modification.ResultsWe here analyze a well-studied model of gene regulatory circuits. A circuit's genotype encodes the regulatory interactions among circuit genes, and its phenotype corresponds to a stable gene activity pattern the circuit forms. For this model, we study how genotypes are arranged in genotype space, where the distance between two genotypes reflects the number of regulatory mutations that set those genotypes apart. Specifically, we address whether this arrangement favors adaptive evolution mediated by plasticity. We find that plasticity facilitates the origin of genotypes that produce a new phenotype in response to non-genetic perturbations. We also find that selection can then stabilize the new phenotype genetically, allowing it to become a circuit's dominant gene expression phenotype. These are generic properties of the circuits we study here.ConclusionsTaken together, our observations suggest that phenotypic plasticity frequently facilitates the evolution of novel beneficial gene activity patterns in gene regulatory circuits.

| S-EPMC3024936 | biostudies-literature

Nests in the cities: adaptive and non-adaptive phenotypic plasticity and convergence in an urban bird.

Project description:Phenotypic plasticity plays a critical role in adaptation to novel environments. Behavioural plasticity enables more rapid responses to unfamiliar conditions than evolution by natural selection. Urban ecosystems are one such novel environment in which behavioural plasticity has been documented. However, whether such plasticity is adaptive, and if plasticity is convergent among urban populations, is poorly understood. We studied the nesting biology of an 'urban-adapter' species, the dark-eyed junco (Junco hyemalis), to understand the role of plasticity in adapting to city life. We examined (i) whether novel nesting behaviours are adaptive, (ii) whether pairs modify nest characteristics in response to prior outcomes, and (iii) whether two urban populations exhibit similar nesting behaviour. We monitored 170 junco nests in urban Los Angeles and compared our results with prior research on 579 nests from urban San Diego. We found that nests placed in ecologically novel locations (off-ground and on artificial surfaces) increased fitness, and that pairs practiced informed re-nesting in site selection. The Los Angeles population more frequently nested off-ground than the San Diego population and exhibited a higher success rate. Our findings suggest that plasticity facilitates adaptation to urban environments, and that the drivers behind novel nesting behaviours are complex and multifaceted.

| S-EPMC7779513 | biostudies-literature

Targeting tumor phenotypic plasticity and metabolic remodeling in adaptive cross-drug tolerance.

Project description:Metastable phenotypic state transitions in cancer cells can lead to the development of transient adaptive resistance or tolerance to chemotherapy. Here, we report that the acquisition of a phenotype marked by increased abundance of CD44 (CD44Hi) by breast cancer cells as a tolerance response to routinely used cytotoxic drugs, such as taxanes, activated a metabolic switch that conferred tolerance against unrelated standard-of-care chemotherapeutic agents, such as anthracyclines. We characterized the sequence of molecular events that connected the induced CD44Hi phenotype to increased activity of both the glycolytic and oxidative pathways and glucose flux through the pentose phosphate pathway (PPP). When given in a specific order, a combination of taxanes, anthracyclines, and inhibitors of glucose-6-phosphate dehydrogenase (G6PD), an enzyme involved in glucose metabolism, improved survival in mouse models of breast cancer. The same sequence of the three-drug combination reduced the viability of patient breast tumor samples in an explant system. Our findings highlight a convergence between phenotypic and metabolic state transitions that confers a survival advantage to cancer cells against clinically used drug combinations. Pharmacologically targeting this convergence could overcome cross-drug tolerance and could emerge as a new paradigm in the treatment of cancer.

| S-EPMC7261372 | biostudies-literature

Functional traits and phenotypic plasticity modulate species coexistence across contrasting climatic conditions.

Project description:Functional traits are expected to modulate plant competitive dynamics. However, how traits and their plasticity in response to contrasting environments connect with the mechanisms determining species coexistence remains poorly understood. Here, we couple field experiments under two contrasting climatic conditions to a plant population model describing competitive dynamics between 10 annual plant species in order to evaluate how 19 functional traits, covering physiological, morphological and reproductive characteristics, are associated with species' niche and fitness differences. We find a rich diversity of univariate and multidimensional associations, which highlight the primary role of traits related to water- and light-use-efficiency for modulating the determinants of competitive outcomes. Importantly, such traits and their plasticity promote species coexistence across climatic conditions by enhancing stabilizing niche differences and by generating competitive trade-offs between species. Our study represents a significant advance showing how leading dimensions of plant function connect to the mechanisms determining the maintenance of biodiversity.

| S-EPMC6560116 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data