Compartmentalization of metabolism between cell types in multicellular organisms: a computational perspective

Maintenance of the individual patterns of gene expression in different cell types is required for the differentiation and development of multicellular organisms. Expression of many genes is controlled by Polycomb (PcG) and Trithorax (TrxG) group proteins that act through association with chromatin. PcG/TrxG are assembled on the DNA sequences termed PREs (Polycomb Response Elements), the activity of which can be modulated and switched from repression to activation. In this study, we analyzed the influence of transcriptional read-through on PRE activity switch mediated by the yeast activator GAL4. We show that a transcription terminator inserted between the promoter and PRE doesnt prevent switching of PRE activity from repression to activation. We demonstrate that, independently of PRE orientation, high levels of transcription fail to dislodge PcG/TrxG proteins from PRE in the absence of a terminator. Thus, transcription is not the main factor required for PRE activity switch.

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In vivotissue-specific chromatin profiling inDrosophila melanogasterusing GFP-tagged nuclei

10.1101/2021.03.23.436625 ◽

2021 ◽

Author(s):

Juan Jauregui-Lozano ◽

Kimaya Bakhle ◽

Vikki M. Weake

Keyword(s):

Cell Types ◽

Chromatin Accessibility ◽

Chromatin State ◽

Specific Cell ◽

Histone Marks ◽

The Many ◽

Chromatin Profiling ◽

Photoreceptor Neurons ◽

Multicellular Organisms

AbstractThe chromatin landscape defines cellular identity in multicellular organisms with unique patterns of DNA accessibility and histone marks decorating the genome of each cell type. Thus, profiling the chromatin state of different cell types in an intact organism under disease or physiological conditions can provide insight into how chromatin regulates cell homeostasisin vivo. To overcome the many challenges associated with characterizing chromatin state in specific cell types, we developed an improved approach to isolateDrosophilanuclei tagged with GFP expressed under Gal4/UAS control. Using this protocol, we profiled chromatin accessibility using Omni-ATAC, and examined the distribution of histone marks using ChIP-seq and CUT&Tag in adult photoreceptor neurons. We show that the chromatin landscape of photoreceptors reflects the transcriptional state of these cells, demonstrating the quality and reproducibility of our approach for profiling the transcriptome and epigenome of specific cell types inDrosophila.

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The developmentally regulated ECM glycoprotein ISG plays an essential role in organizing the ECM and orienting the cells of Volvox

Journal of Cell Science ◽

10.1242/jcs.113.24.4605 ◽

2000 ◽

Vol 113 (24) ◽

pp. 4605-4617

Author(s):

A. Hallmann ◽

D.L. Kirk

Keyword(s):

Critical Role ◽

Somatic Cells ◽

Cell Types ◽

Model System ◽

Swimming Behavior ◽

Truncated Form ◽

Developmentally Regulated ◽

Gene Encoding ◽

Ecm Architecture ◽

Multicellular Organisms

Volvox is one of the simplest multicellular organisms with only two cell types, yet it has a surprisingly complex extracellular matrix (ECM) containing many region-specific morphological components, making Volvox suitable as a model system for ECM investigations. ECM deposition begins shortly after inversion, which is the process by which the embryo turns itself right-side-out at the end of embryogenesis. It was previously shown that the gene encoding an ECM glycoprotein called ISG is transcribed very transiently during inversion. Here we show that the developmentally controlled ISG accumulates at the bases of the flagella right after inversion, before any morphologically recognizable ECM structures have yet developed. Later, ISG is abundant in the ‘flagellar hillocks’ that encircle the basal ends of all flagella, and in the adjacent ‘boundary zone’ that delimits the spheroid. Transgenic Volvox were generated which express a truncated form of ISG. These transgenics exhibit a severely disorganized ECM within which the cells are embedded in a highly chaotic manner that precludes motility. A synthetic version of the C-terminal decapeptide of ISG has a similar disorganizing effect, but only when it is applied during or shortly after inversion. We postulate that ISG plays a critical role in morphogenesis and acts as a key organizer of ECM architecture; at the very beginning of ECM formation ISG establishes an essential initial framework that both holds the somatic cells in an adaptive orientation and acts as the scaffold upon which the rest of the ECM can be properly assembled, assuring that somatic cells of post-inversion spheroids are held in orientations and locations that makes adaptive swimming behavior possible.

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Developmentally distinct MYB genes encode functionally equivalent proteins in Arabidopsis

Development ◽

10.1242/dev.128.9.1539 ◽

2001 ◽

Vol 128 (9) ◽

pp. 1539-1546 ◽

Cited By ~ 7

Author(s):

M.M. Lee ◽

J. Schiefelbein

Keyword(s):

Functional Relationship ◽

Expression Patterns ◽

Cell Types ◽

Myb Transcription Factor ◽

Regulatory Sequences ◽

Myb Gene ◽

Distinct Cell ◽

Transcription Factor Genes ◽

Myb Genes ◽

Multicellular Organisms

The duplication and divergence of developmental control genes is thought to have driven morphological diversification during the evolution of multicellular organisms. To examine the molecular basis of this process, we analyzed the functional relationship between two paralogous MYB transcription factor genes, WEREWOLF (WER) and GLABROUS1 (GL1), in Arabidopsis. The WER and GL1 genes specify distinct cell types and exhibit non-overlapping expression patterns during Arabidopsis development. Nevertheless, reciprocal complementation experiments with a series of gene fusions showed that WER and GL1 encode functionally equivalent proteins, and their unique roles in plant development are entirely due to differences in their cis-regulatory sequences. Similar experiments with a distantly related MYB gene (MYB2) showed that its product cannot functionally substitute for WER or GL1. Furthermore, an analysis of the WER and GL1 proteins shows that conserved sequences correspond to specific functional domains. These results provide new insights into the evolution of the MYB gene family in Arabidopsis, and, more generally, they demonstrate that novel developmental gene function may arise solely by the modification of cis-regulatory sequences.

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A systems perspective of heterocellular signaling

Essays in Biochemistry ◽

10.1042/ebc20180015 ◽

2018 ◽

Vol 62 (4) ◽

pp. 607-617 ◽

Cited By ~ 3

Author(s):

Alan Wells ◽

H. Steven Wiley

Keyword(s):

Cell Types ◽

Regulatory Processes ◽

Technical Developments ◽

Building Models ◽

Realistic Description ◽

Multiple Cell ◽

Solid Foundation ◽

And Function ◽

Multicellular Organisms ◽

Different Cell Types

Signal exchange between different cell types is essential for development and function of multicellular organisms, and its dysregulation is causal in many diseases. Unfortunately, most cell-signaling work has employed single cell types grown under conditions unrelated to their native context. Recent technical developments have started to provide the tools needed to follow signaling between multiple cell types, but gaps in the information they provide have limited their usefulness in building realistic models of heterocellular signaling. Currently, only targeted assays have the necessary sensitivity, selectivity, and spatial resolution to usefully probe heterocellular signaling processes, but these are best used to test specific, mechanistic models. Decades of systems biology research with monocultures has provided a solid foundation for building models of heterocellular signaling, but current models lack a realistic description of regulated proteolysis and the feedback processes triggered within and between cells. Identification and understanding of key regulatory processes in the extracellular environment and of recursive signaling patterns between cells will be essential to building predictive models of heterocellular systems.

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Developmental decisions in Aspergillus nidulans are modulated by Ras activity.

Molecular and Cellular Biology ◽

10.1128/mcb.14.8.5333 ◽

1994 ◽

Vol 14 (8) ◽

pp. 5333-5348 ◽

Cited By ~ 87

Author(s):

T Som ◽

V S Kolaparthi

Keyword(s):

Aspergillus Nidulans ◽

Essential Gene ◽

Cell Types ◽

Tube Formation ◽

Stage Of Development ◽

Initial Stage ◽

Concentration Threshold ◽

High Level ◽

Multicellular Organisms ◽

Further Development

To better understand how Ras controls development of multicellular organisms, we have chosen Aspergillus nidulans as a model system. When grown on solid medium, this fungus follows a well-defined program of development, sequentially giving rise to several cell types which produce three distinct structures: vegetative hyphae, aerial hyphae, and the conidiophore structure. Here we describe a ras homolog found in this fungus (Aras) and demonstrate that it is an essential gene that regulates the ordered program of development. We created dominant alleles of this gene and expressed them to different levels in order to vary the ratio of GTP-bound (active) to GDP-bound (inactive) A-Ras protein. When the amount of active Ras is large, nuclear division proceeds, but further development is inhibited at the early step of germ tube formation. At an intermediate level of active Ras, aerial hypha formation is inhibited, while at a low level, conidiophore formation is inhibited. Maintenance of an even lower level of the active Ras is essential for initiation and progression of conidiophore formation, the final stage of development. When the level of active Ras is artificially lowered, each stage of development is initiated prematurely except germination, the initial stage of development. Therefore, the progression of the ordered developmental pathway of A. nidulans is dependent upon an initial high level of active Ras followed by its gradual decrease. We propose that several concentration threshold exist, each of which allows development to proceed to a certain point, producing the proper cell type while inhibiting further development.

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Universal principles of lineage architecture and stem cell identity in renewing tissues

10.1101/2020.03.10.984898 ◽

2020 ◽

Author(s):

Philip Greulich ◽

Ben D. MacArthur ◽

Cristina Parigini ◽

Rubén J. Sánchez-García

Keyword(s):

Stem Cell ◽

Cell Lineage ◽

Adult Stem Cell ◽

Feedback Regulation ◽

Cell Types ◽

Universal Principles ◽

Formal Framework ◽

Cell Niche ◽

Multicellular Organisms ◽

The Relationship

Adult tissues in multicellular organisms typically contain a variety of stem, progenitor and differentiated cell types arranged in a lineage hierarchy that regulates healthy tissue turnover and repair. Lineage hierarchies in disparate tissues often exhibit common features, yet the general principles regulating their architecture are not known. Here, we provide a formal framework for understanding the relationship between cell molecular ‘states’ (patterns of gene, protein expression etc. in the cell) and cell ‘types’ that uses notions from network science to decompose the structure of cell state trajectories into functional units. Using this framework we show that many widely experimentally observed features of cell lineage architectures – including the fact that a single adult stem cell type always resides at the apex of a lineage hierarchy – arise as a natural consequence of homeostasis, and indeed are the only possible way that lineage architectures can be constructed to support homeostasis in renewing tissues. Furthermore, under suitable feedback regulation, for example from the stem cell niche, we show that the property of ‘stemness’ is entirely determined by the cell environment. Thus, we argue that stem cell identities are contextual and not determined by hard-wired, cell-intrinsic, characteristics.

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Complex Organization in Multicellularity as a Necessity in Evolution

Artificial Life ◽

10.1162/106454600300103638 ◽

2000 ◽

Vol 6 (4) ◽

pp. 265-281 ◽

Cited By ~ 16

Author(s):

Chikara Furusawa ◽

Kunihiko Kaneko

Keyword(s):

Developmental Process ◽

Cell Types ◽

Chemical Diversity ◽

Growth Speed ◽

Multipotent Stem Cells ◽

Use Of Resources ◽

Complex Organization ◽

Development And Differentiation ◽

System Robustness ◽

Multicellular Organisms

By introducing a dynamical system model of a multicellular system, it is shown that an organism with a variety of differentiated cell types and a complex pattern emerges through cell-cell interactions even without postulating any elaborate control mechanism. Such an organism is found to maintain a larger growth speed as an ensemble, by achieving a cooperative use of resources, than do simple homogeneous cells, which behave “selfishly.” This suggests that the emergence of multicellular organisms with complex organization is a necessity in evolution. According to our theoretical model, there initially appear multipotent stem cells, which undergo stochastic differentiation to other cell types. With development and differentiation, both the chemical diversity and the complexity of intra-cellular dynamics are decreased, as a general consequence of our system. Robustness of the developmental process is also confirmed.

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Developmental decisions in Aspergillus nidulans are modulated by Ras activity

Molecular and Cellular Biology ◽

10.1128/mcb.14.8.5333-5348.1994 ◽

1994 ◽

Vol 14 (8) ◽

pp. 5333-5348

Author(s):

T Som ◽

V S Kolaparthi

Keyword(s):

Aspergillus Nidulans ◽

Essential Gene ◽

Cell Types ◽

Tube Formation ◽

Stage Of Development ◽

Initial Stage ◽

Concentration Threshold ◽

High Level ◽

Multicellular Organisms ◽

Further Development

To better understand how Ras controls development of multicellular organisms, we have chosen Aspergillus nidulans as a model system. When grown on solid medium, this fungus follows a well-defined program of development, sequentially giving rise to several cell types which produce three distinct structures: vegetative hyphae, aerial hyphae, and the conidiophore structure. Here we describe a ras homolog found in this fungus (Aras) and demonstrate that it is an essential gene that regulates the ordered program of development. We created dominant alleles of this gene and expressed them to different levels in order to vary the ratio of GTP-bound (active) to GDP-bound (inactive) A-Ras protein. When the amount of active Ras is large, nuclear division proceeds, but further development is inhibited at the early step of germ tube formation. At an intermediate level of active Ras, aerial hypha formation is inhibited, while at a low level, conidiophore formation is inhibited. Maintenance of an even lower level of the active Ras is essential for initiation and progression of conidiophore formation, the final stage of development. When the level of active Ras is artificially lowered, each stage of development is initiated prematurely except germination, the initial stage of development. Therefore, the progression of the ordered developmental pathway of A. nidulans is dependent upon an initial high level of active Ras followed by its gradual decrease. We propose that several concentration threshold exist, each of which allows development to proceed to a certain point, producing the proper cell type while inhibiting further development.

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A Protein Important for Antimicrobial Peptide Resistance, YdeI/OmdA, Is in the Periplasm and Interacts with OmpD/NmpC

Journal of Bacteriology ◽

10.1128/jb.00688-09 ◽

2009 ◽

Vol 191 (23) ◽

pp. 7243-7252 ◽

Cited By ~ 36

Author(s):

M. Carolina Pilonieta ◽

Kimberly D. Erickson ◽

Robert K. Ernst ◽

Corrella S. Detweiler

Keyword(s):

Gene Expression ◽

Antimicrobial Peptide ◽

Bacterial Resistance ◽

Cell Types ◽

Polymyxin B ◽

Sensor Kinase ◽

Multiple Cell ◽

Ob Fold ◽

Antimicrobial Peptide Resistance ◽

Multicellular Organisms

ABSTRACT Antimicrobial peptides (AMPs) kill or prevent the growth of microbes. AMPs are made by virtually all single and multicellular organisms and are encountered by bacteria in diverse environments, including within a host. Bacteria use sensor-kinase systems to respond to AMPs or damage caused by AMPs. Salmonella enterica deploys at least three different sensor-kinase systems to modify gene expression in the presence of AMPs: PhoP-PhoQ, PmrA-PmrB, and RcsB-RcsC-RcsD. The ydeI gene is regulated by the RcsB-RcsC-RcsD pathway and encodes a 14-kDa predicted oligosaccharide/oligonucleotide binding-fold (OB-fold) protein important for polymyxin B resistance in broth and also for virulence in mice. We report here that ydeI is additionally regulated by the PhoP-PhoQ and PmrA-PmrB sensor-kinase systems, which confer resistance to cationic AMPs by modifying lipopolysaccharide (LPS). ydeI, however, is not important for known LPS modifications. Two independent biochemical methods found that YdeI copurifies with OmpD/NmpC, a member of the trimeric β-barrel outer membrane general porin family. Genetic analysis indicates that ompD contributes to polymyxin B resistance, and both ydeI and ompD are important for resistance to cathelicidin antimicrobial peptide, a mouse AMP produced by multiple cell types and expressed in the gut. YdeI localizes to the periplasm, where it could interact with OmpD. A second predicted periplasmic OB-fold protein, YgiW, and OmpF, another general porin, also contribute to polymyxin B resistance. Collectively, the data suggest that periplasmic OB-fold proteins can interact with porins to increase bacterial resistance to AMPs.

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