scholarly journals Ligand-receptor promiscuity enables cellular addressing

2020 ◽  
Author(s):  
Christina J. Su ◽  
Arvind Murugan ◽  
James M. Linton ◽  
Akshay Yeluri ◽  
Justin Bois ◽  
...  
Keyword(s):  
Cell Fate ◽  
Control Cell ◽  
Cell Communication ◽  
Biochemical Parameter ◽  
Cell Types ◽  
Receptor Expression ◽  
Modeling Framework ◽  
Morphogenetic Protein ◽  
Bmp Pathway ◽  
Fate Decision

AbstractIn multicellular organisms, secreted ligands selectively activate, or “address,” specific target cell populations to control cell fate decision-making and other processes. Key cell-cell communication pathways use multiple promiscuously interacting ligands and receptors, provoking the question of how addressing specificity can emerge from molecular promiscuity. To investigate this issue, we developed a general mathematical modeling framework based on the bone morphogenetic protein (BMP) pathway architecture. We find that promiscuously interacting ligand-receptor systems allow a small number of ligands, acting in combinations, to address a larger number of individual cell types, each defined by its receptor expression profile. Promiscuous systems outperform seemingly more specific one-to-one signaling architectures in addressing capacity. Combinatorial addressing extends to groups of cell types, is robust to receptor expression noise, grows more powerful with increasing receptor multiplicity, and is maximized by specific biochemical parameter relationships. Together, these results identify fundamental design principles governing cell addressing by ligand combinations.

scholarly journals Recent advances in understanding female gametophyte development

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 804 ◽  
Author(s):  
Debra J Skinner ◽  
Venkatesan Sundaresan
Keyword(s):  
Cell Fate ◽  
Female Gametophyte ◽  
Cell Communication ◽  
Embryo Sac ◽  
Cell Types ◽  
Egg Cell ◽  
Male Gametes ◽  
Reproductive Unit ◽  
Genetic Mechanisms ◽  
Female Gametophyte Development

The haploid female gametophyte (embryo sac) is an essential reproductive unit of flowering plants, usually comprising four specialized cell types, including the female gametes (egg cell and central cell). The differentiation of these cells relies on spatial signals which pattern the gametophyte along a proximal-distal axis, but the molecular and genetic mechanisms by which cell identities are determined in the embryo sac have long been a mystery. Recent identification of key genes for cell fate specification and their relationship to hormonal signaling pathways that act on positional cues has provided new insights into these processes. A model for differentiation can be devised with egg cell fate as a default state of the female gametophyte and with other cell types specified by the action of spatially regulated factors. Cell-to-cell communication within the gametophyte is also important for maintaining cell identity as well as facilitating fertilization of the female gametes by the male gametes (sperm cells).

scholarly journals Stochastic antagonism between two proteins governs a bacterial cell fate switch

Science ◽  
2019 ◽  
Vol 366 (6461) ◽  
pp. 116-120 ◽  
Author(s):  
Nathan D. Lord ◽  
Thomas M. Norman ◽  
Ruoshi Yuan ◽  
Somenath Bakshi ◽  
Richard Losick ◽  
...  
Keyword(s):  
Cell Fate ◽  
Regulatory Networks ◽  
Cell Types ◽  
Feedback Loops ◽  
Cell Fate Determination ◽  
Cell Fate Decision ◽  
A Cell ◽  
Fate Decision ◽  
Antagonistic Interactions

Cell fate decision circuits must be variable enough for genetically identical cells to adopt a multitude of fates, yet ensure that these states are distinct, stably maintained, and coordinated with neighboring cells. A long-standing view is that this is achieved by regulatory networks involving self-stabilizing feedback loops that convert small differences into long-lived cell types. We combined regulatory mutants and in vivo reconstitution with theory for stochastic processes to show that the marquee features of a cell fate switch in Bacillus subtilis—discrete states, multigenerational inheritance, and timing of commitments—can instead be explained by simple stochastic competition between two constitutively produced proteins that form an inactive complex. Such antagonistic interactions are commonplace in cells and could provide powerful mechanisms for cell fate determination more broadly.

scholarly journals Bone Morphogenetic Protein/SMAD Signaling Orients Cell Fate Decision by Impairing KSRP-Dependent MicroRNA Maturation

Cell Reports ◽  
2012 ◽  
Vol 2 (5) ◽  
pp. 1159-1168 ◽  
Author(s):  
Michela Pasero ◽  
Matteo Giovarelli ◽  
Gabriele Bucci ◽  
Roberto Gherzi ◽  
Paola Briata
Keyword(s):  
Bone Morphogenetic Protein ◽  
Cell Fate ◽  
Cell Fate Decision ◽  
Smad Signaling ◽  
Morphogenetic Protein ◽  
Fate Decision

scholarly journals Epigenetic Control of Mesenchymal Stromal Cell Fate Decision

2021 ◽  
Author(s):  
Haoli Ying ◽  
Ruolang Pan ◽  
Ye Chen
Keyword(s):  
Cell Fate ◽  
Molecular Mechanisms ◽  
Epigenetic Modification ◽  
Cell Types ◽  
Connective Tissues ◽  
Differentiation Potential ◽  
Cell Fate Decisions ◽  
Fate Decision ◽  
Msc Differentiation

Mesenchymal stem cells (MSCs) are progenitors of connective tissues, which have emerged as important tools for tissue engineering owing to their differentiation potential in various cell types. The therapeutic utility of MSCs hinges upon our understanding of the molecular mechanisms involved in cellular fate decisions. Thus, the elucidation of the regulation of MSC differentiation has attracted increasing attention in recent years. A variety of external cues contribute to the process of MSC differentiation, including chemical, physical, and biological factors. Among the multiple factors that are known to affect cell fate decisions, the epigenetic regulation of MSC differentiation has become a research hotspot. In this chapter, we summarize recent progress in the determination of the effects of epigenetic modification on the multilineage differentiation of MSCs.

scholarly journals ICELLNET: a transcriptome-based framework to dissect intercellular communication

2020 ◽  
Author(s):  
Floriane Noël ◽  
Lucile Massenet-Regad ◽  
Irit Carmi-Levy ◽  
Antonio Cappuccio ◽  
Maximilien Grandclaudon ◽  
...  
Keyword(s):  
Cell Population ◽  
Cell Communication ◽  
Cell Types ◽  
Receptor Expression ◽  
Global Integration ◽  
Cancer Associated Fibroblast ◽  
Receptor Interactions ◽  
Biological Interpretation ◽  
A Cell ◽  
Multiple Cell

AbstractCell-to-cell communication can be inferred from ligand-receptor expression in cell transcriptomic datasets. However, important challenges remain: 1) global integration of cell-to-cell communication, 2) biological interpretation, and 3) application to individual cell population transcriptomic profiles. We developed ICELLNET, a transcriptomic-based framework integrating: 1) an original expert-curated database of ligand-receptor interactions accounting for multiple subunits expression, 2) quantification of communication scores, 3) the possibility to connect a cell population of interest with 31 reference human cell types (BioGPS), and 4) three visualization modes to facilitate biological interpretation. We applied ICELLNET to uncover different communication in breast cancer associated fibroblast (CAF) subsets. ICELLNET also revealed autocrine IL-10 as a switch to control human dendritic cell communication with up to 12 other cell types, four of which were experimentally validated. In summary, ICELLNET is a global, versatile, biologically validated, and easy-to-use framework to dissect cell communication from single or multiple cell-based transcriptomic profile(s).

scholarly journals Role of metabolic spatiotemporal dynamics in regulating biofilm colony expansion

2018 ◽  
Vol 115 (16) ◽  
pp. 4288-4293 ◽  
Author(s):  
Federico Bocci ◽  
Yoko Suzuki ◽  
Mingyang Lu ◽  
José N. Onuchic
Keyword(s):  
Cell Fate ◽  
Biological Networks ◽  
Cell Communication ◽  
Spatiotemporal Dynamics ◽  
Cell Populations ◽  
Modeling Framework ◽  
Oscillatory Dynamics ◽  
Oscillatory Dynamic ◽  
Cell Cell

Cell fate determination is typically regulated by biological networks, yet increasing evidences suggest that cell−cell communication and environmental stresses play crucial roles in the behavior of a cell population. A recent microfluidic experiment showed that the metabolic codependence of two cell populations generates a collective oscillatory dynamic during the expansion of aBacillus subtilisbiofilm. We develop a modeling framework for the spatiotemporal dynamics of the associated metabolic circuit for cells in a colony. We elucidate the role of metabolite diffusion and the need of two distinct cell populations to observe oscillations. Uniquely, this description captures the onset and thereafter stable oscillatory dynamics during expansion and predicts the existence of damping oscillations under various environmental conditions. This modeling scheme provides insights to understand how cells integrate the information from external signaling and cell−cell communication to determine the optimal survival strategy and/or maximize cell fitness in a multicellular system.

scholarly journals The context-dependent, combinatorial logic of BMP signaling

2020 ◽  
Author(s):  
Heidi Klumpe ◽  
Matthew A. Langley ◽  
James M. Linton ◽  
Christina J. Su ◽  
Yaron E. Antebi ◽  
...  
Keyword(s):  
Communication Systems ◽  
Cell Communication ◽  
Bmp Signaling ◽  
Receptor Expression ◽  
Signaling Systems ◽  
Morphogenetic Protein ◽  
Pathway Activation ◽  
Ligand Interactions ◽  
Context Dependent ◽  
Combinatorial Interactions

SummaryCell-cell communication systems typically comprise families of ligand and receptor variants that function together in combinations. Pathway activation depends in a complex way on which ligands are present and what receptors are expressed by the signal-receiving cell. To understand the combinatorial logic of such a system, we systematically measured pairwise Bone Morphogenetic Protein (BMP) ligand interactions in cells with varying receptor expression. Ligands could be classified into equivalence groups based on their profile of positive and negative synergies with other ligands. These groups varied with receptor expression, explaining how ligands can functionally replace each other in one context but not another. Context-dependent combinatorial interactions could be explained by a biochemical model based on competitive formation of alternative signaling complexes with distinct activities. Together, these results provide insights into the roles of BMP combinations in developmental and therapeutic contexts and establish a framework for analyzing other combinatorial, context-dependent signaling systems.

Gonadal mesoderm and fat body initially follow a common developmental path in Drosophila

Development ◽  
1998 ◽  
Vol 125 (5) ◽  
pp. 837-844 ◽  
Author(s):  
L.A. Moore ◽  
H.T. Broihier ◽  
M. Van Doren ◽  
R. Lehmann
Keyword(s):  
Cell Fate ◽  
Fat Body ◽  
Cell Types ◽  
Drosophila Embryo ◽  
Body Development ◽  
Developmental Relationship ◽  
Close Juxtaposition ◽  
Fate Decision ◽  
Different Cell Types ◽  
Lateral Mesoderm

During gastrulation, the Drosophila mesoderm invaginates and forms a single cell layer in close juxtaposition to the overlying ectoderm. Subsequently, particular cell types within the mesoderm are specified along the anteroposterior and dorsoventral axes. The exact developmental pathways that guide the specification of different cell types within the mesoderm are not well understood. We have analyzed the developmental relationship between two mesodermal tissues in the Drosophila embryo, the gonadal mesoderm and the fat body. Both tissues arise from lateral mesoderm within the eve domain. Whereas in the eve domain of parasegments 10–12 gonadal mesoderm develops from dorsolateral mesoderm and fat body from ventrolateral mesoderm, in parasegments 4–9 only fat body is specified. Our results demonstrate that the cell fate decision between gonadal mesoderm and fat body identity within dorsolateral mesoderm along the anteroposterior axis is determined by the combined actions of genes including abdA, AbdB and srp; while srp promotes fat body development, abdA allows gonadal mesoderm to develop by repressing srp function. Furthermore, we present evidence from genetic analysis suggesting that, before stage 10 of embryogenesis, gonadal mesoderm and the fat body have not yet been specified as different cell types, but exist as a common pool of precursor cells requiring the functions of the tin, zfh-1 and cli genes for their development.

scholarly journals Spatiotemporal cellular movement and fate decisions during first pharyngeal arch morphogenesis

2020 ◽  
Vol 6 (51) ◽  
pp. eabb0119
Author(s):  
Yuan Yuan ◽  
Yong-hwee Eddie Loh ◽  
Xia Han ◽  
Jifan Feng ◽  
Thach-Vu Ho ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Cell Fate ◽  
Compartment Model ◽  
Cell Types ◽  
Pharyngeal Arch ◽  
Cell Fate Decision ◽  
Fate Decision ◽  
Fate Restriction ◽  
Different Cell Types ◽  
Cellular Movement

Cranial neural crest (CNC) cells contribute to different cell types during embryonic development. It is unknown whether postmigratory CNC cells undergo dynamic cellular movement and how the process of cell fate decision occurs within the first pharyngeal arch (FPA). Our investigations demonstrate notable heterogeneity within the CNC cells, refine the patterning domains, and identify progenitor cells within the FPA. These progenitor cells undergo fate bifurcation that separates them into common progenitors and mesenchymal cells, which are characterized by Cdk1 and Spry2/Notch2 expression, respectively. The common progenitors undergo further bifurcations to restrict them into osteogenic/odontogenic and chondrogenic/fibroblast lineages. Disruption of a patterning domain leads to specific mandible and tooth defects, validating the binary cell fate restriction process. Different from the compartment model of mandibular morphogenesis, our data redefine heterogeneous cellular domains within the FPA, reveal dynamic cellular movement in time, and describe a sequential series of binary cell fate decision-making process.

scholarly journals Single cell response landscape of graded Nodal signaling in zebrafish explants

2021 ◽  
Author(s):  
Tao Cheng ◽  
Yanyi Xing ◽  
Yunfei Li ◽  
Cong Liu ◽  
Ying Huang ◽  
...  
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Cell Response ◽  
Expression Patterns ◽  
Cell Types ◽  
Nodal Signaling ◽  
Animal Pole ◽  
Fate Decision ◽  
Single Cell Response

Nodal, as a morphogen, plays important roles in cell fate decision, pattern formation and organizer function. But because of the complex context in vivo and technology limitations, systematic studying of genes, cell types and patterns induced by Nodal alone is still missing. Here, by using a relatively simplified model, the zebrafish blastula animal pole explant avoiding additional instructive signals and prepatterns, we constructed a single cell response landscape of graded Nodal signaling, identified 105 Nodal immediate targets and depicted their expression patterns. Our results show that Nodal signaling is sufficient to induce anterior-posterior patterned axial mesoderm and head structure. Surprisingly, the endoderm induced by Nodal alone is mainly the anterior endoderm which gives rise to the pharyngeal pouch only, but not internal organs. Among the 105 Nodal targets, we identified 14 genes carrying varying levels of axis induction capability. Overall, our work provides new insights for understanding of the Nodal function and a valuable resource for future studies of patterning and morphogenesis induced by it.

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