Three faces of biofilms: a microbial lifestyle, a nascent multicellular organism, and an incubator for diversity

Biofilms are organised heterogeneous assemblages of microbial cells that are encased within a self-produced matrix. Current estimates suggest that up to 80% of bacterial and archaeal cells reside in biofilms. Since biofilms are the main mode of microbial life, understanding their biology and functions is critical, especially as controlling biofilm growth is essential in industrial, infrastructure and medical contexts. Here we discuss biofilms both as collections of individual cells, and as multicellular biological individuals, and introduce the concept of biofilms as unique incubators of diversity for the microbial world.

Cell division in the shoot apical meristem is a trigger for miR156 decline and vegetative phase transition in Arabidopsis

What determines the rate at which a multicellular organism matures is a fundamental question in biology. In plants, the decline of miR156 with age serves as an intrinsic, evolutionarily conserved timer for the juvenile-to-adult phase transition. However, the way in which age regulates miR156 abundance is poorly understood. Here, we show that the rate of decline in miR156 is correlated with developmental age rather than chronological age. Mechanistically, we found that cell division in the apical meristem is a trigger for miR156 decline. The transcriptional activity of MIR156 genes is gradually attenuated by the deposition of the repressive histone mark H3K27me3 along with cell division. Our findings thus provide a plausible explanation of why the maturation program of a multicellular organism is unidirectional and irreversible under normal growth conditions and suggest that cell quiescence is the fountain of youth in plants.

Whole transcriptome sequencing identifies key circRNAs, lncRNAs, and miRNAs regulating neurogenesis in developing mouse retina

Background The molecular complexity of neural retina development remains poorly studied. Knowledge of retinal neurogenesis regulation sheds light on retinal degeneration therapy exploration. Therefore, we integrated the time-series circRNA, lncRNA, miRNA, and mRNA expression profiles of the developing retina through whole-transcriptome sequencing. The key functional ncRNAs and the ceRNA network regulating retinal neurogenesis were identified. Results Transcriptomic analysis identified circRNA as the most variable ncRNA subtype. We screened a series of neurogenesis-related circRNAs, lncRNAs, and miRNAs using different strategies based on their diversified molecular functions. The expression of circCDYL, circATXN1, circDYM, circPRGRIP, lncRNA Meg3, and lncRNA Vax2os was validated by quantitative real-time PCR. These circRNAs and lncRNAs participate in neurotransmitter transport and multicellular organism growth through the intricate circRNA/lncRNA-miRNA-mRNA network. Conclusion Whole-transcriptome sequencing and bioinformatics analysis systematically screened key ncRNAs in retinal neurogenesis. The validated ncRNAs and their circRNA/lncRNA-miRNA-mRNA network involve neurotransmitter transport and multicellular organism growth during retinal development.

Evolution of irreversible somatic differentiation

A key innovation emerging in complex animals is irreversible somatic differentiation: daughters of a vegetative cell perform a vegetative function as well, thus, forming a somatic lineage that can no longer be directly involved in reproduction. Primitive species use a different strategy: vegetative and reproductive tasks are separated in time rather than in space. Starting from such a strategy, how is it possible to evolve life forms which use some of their cells exclusively for vegetative functions? Here, we develop an evolutionary model of development of a simple multicellular organism and find that three components are necessary for the evolution of irreversible somatic differentiation: (i) costly cell differentiation, (ii) vegetative cells that significantly improve the organism’s performance even if present in small numbers, and (iii) large enough organism size. Our findings demonstrate how an egalitarian development typical for loose cell colonies can evolve into germ-soma differentiation dominating metazoans.

Breaking symmetry: the asymmetries in epigenetic inheritance

Symmetry and asymmetry are the fundamental aspects of life. Most cells within a multicellular organism contain the same genetic information, passed on from one originating cell, the zygote; however, these cells can take on a variety of different identities, with diverse appearances and functions. A fundamental question in biology ponders how cells containing identical DNA content can take on different cell identities. Epigenetic mechanisms could be the symmetry-breaking factor, as they are able to change the gene expression in cells without changing the DNA sequence. While the process of duplication and segregation of DNA during cell division has been well studied, it is less understood how the epigenetic information is established and inherited in the cells within a multicellular organism. Studies of asymmetric stem cell division, where a stem cell division gives rise to a self-renewed stem cell and a differentiating daughter cell, provide a model to study how epigenetic information is maintained or changed to produce daughter cells with identical genetic information but distinct cell fates. Here, we discuss the findings and ideas of how epigenetic information is maintained or changed during asymmetric cell division and the importance of this asymmetry in influencing cell fate.

Evolution of irreversible somatic differentiation

A key innovation emerging in complex animals is irreversible somatic differentiation: daughters of a vegetative cell perform a vegetative function as well, thus, forming a somatic lineage that can no longer be directly involved in reproduction. Primitive species use a different strategy: vegetative and reproductive tasks are separated in time rather than in space. Starting from such a strategy, how is it possible to evolve life forms which use some of their cells exclusively for vegetative functions? Here, we developed an evolutionary model of development of a simple multicellular organism and found that three components are necessary for the evolution of irreversible somatic differentiation: (i) costly cell differentiation, (ii) vegetative cells that significantly improve the organism’s performance even if present in small numbers, and (iii) large enough organism size. Our findings demonstrate how an egalitarian development typical for loose cell colonies can evolve into germ-soma differentiation dominating metazoans.

Genetically encoded ratiometric biosensor for probing lysosomal pH in mammalian cells and C. elegans

ABSTRACTLysosomes are important sites for macromolecular degradation, defined by a profoundly acidic lumenal pH of ~4.5. To better understand lysosomal pH, we designed a novel, genetically encoded, fluorescent protein-based pH biosensor called FIRE-pHLy (Fluorescence Indicator REporting pH in Lysosomes). This sensor was targeted to lysosomes with LAMP1 and reported lumenal pH between 3.0 and 6.0 with monomeric teal fluorescent protein 1 (mTFP1), a bright cyan FP variant with a pKa of 4.3. Ratiometric quantification was enabled with cytosolically oriented mCherry using high-content imaging. We expressed FIRE-pHLy in several cellular models as well as the multicellular organism C. elegans and quantified its alkalinizing response to bafilomycin A1, a specific V-ATPase inhibitor. In summary, we have engineered FIRE-pHLy, a specific, robust and versatile lysosomal pH biosensor that has broad applications for investigating pH dynamics in aging and lysosome-related diseases, as well as in lysosome-based drug discovery.

Intercellular Mitochondrial Transfer in the Tumor Microenvironment

Cell-to-cell communication is a fundamental process in every multicellular organism. In addition to membrane-bound and released factors, the sharing of cytosolic components represents a new, poorly explored signaling route. An extraordinary example of this communication channel is the direct transport of mitochondria between cells. In this review, we discuss how intercellular mitochondrial transfer can be used by cancer cells to sustain their high metabolic requirements and promote drug resistance and describe relevant molecular players in the context of current and future cancer therapy.

The cell

The cell is a dynamic entity. Cells are not simply building blocks that are linked together to create an organism: each cell comprises a dynamic network of interacting macromolecules. Just how dynamic has been brought home by recent advances in cell imaging technologies. A host of multisubunit molecular structures must assemble and disassemble in a highly coordinated, exquisitely regulated, and beautifully choreographed manner to ensure the integrity of the cell and provide its ability to function correctly as a single unit within a large multicellular organism. This chapter explains how the cell is the fundamental unit of all forms of independent life on this planet, from the simplest single-celled prokaryote to the most complex multicellular eukaryote.