Current Opinion in Cell Biology

High-throughput approaches for the analysis of extrinsic regulators of stem cell fate.

Publication Date: 2012 Jan 31 PMID: 22301436
Authors: Ranga, A. - Lutolf, M. P.
Journal: Curr Opin Cell Biol

The complexity of stem cell niches poses a tremendous challenge to understanding mechanisms of extrinsic regulation of stem cell fate. In order to better understand niche signaling and its effect on stem cell fate choices, in vitro systems are being engineered which recapitulate, in a simplistic but increasingly sophisticated manner, native stem cell niches. New technologies or new combinations of existing technologies allow more systematic ways to probe niche signaling in high-throughput. Systems biology approaches in experimental design, data acquisition and analysis will be necessary to tackle the challenges that lie ahead.

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From stem cells to cancer stem cells: HIF takes the stage.

Publication Date: 2012 Jan 30 PMID: 22296771
Authors: Lee, K. E. - Simon, M. C.
Journal: Curr Opin Cell Biol

Hypoxia, a condition of insufficient oxygen availability, occurs during normal development as well as tumorigenesis. Cellular responses to hypoxia are primarily mediated by hypoxia-inducible factors (HIFs). Recent studies have revealed that dormant hematopoietic stem cells (HSCs) reside within hypoxic regions of the bone marrow and that HIF is a critical player in HSC homeostasis. The functional significance of HIF in maintaining stemness also applies to cancer stem cells in hematological malignancies. These findings indicate that better understanding of the mechanisms underlying HIF functions in stem cells should permit the development of new therapies for tissue regeneration and cancer.

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Local signaling within stem cell niches: insights from Drosophila.

Publication Date: 2012 Jan 30 PMID: 22296770
Authors: Resende, L. P. - Jones, D. L.
Journal: Curr Opin Cell Biol

Tissue stem cells are found in specialized microenvironments (niches) where they are exposed to diverse systemic and local signals that are integrated with cell intrinsic factors to regulate stem cell behavior. In general, systemic signals are utilized to coordinate the response of tissues to acute or long-term changes that affect the whole organism, such as variations in nutrient availability or aging. In contrast, local signaling regulates tissue maintenance by balancing stem cell self-renewal with differentiation under homeostatic conditions and in response to local damage. In this review, we highlight the role of the JAK-STAT pathway in two Drosophila stem cell systems, the testis and intestine, and compare and contrast how activation of this pathway leads to tissue maintenance under both homeostatic conditions and in response to stress or injury.

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Cilia, KIF3 molecular motor and nodal flow.

Publication Date: 2012 Jan 27 PMID: 22285930
Authors: Hirokawa, N. - Tanaka, Y. - Okada, Y.
Journal: Curr Opin Cell Biol

The establishment of left-right asymmetry during development of vertebrate embryos depends on leftward flow in the nodal cavity. The flow is produced by the rotational movement of the posteriorly tilted nodal cilia. However, it remains poorly understood how the nodal cilia are tilted posteriorly, and how the directionality of the flow is translated into gene expression patterns in the embryo. Recent studies have identified signaling molecules involved in these processes. First, planar cell polarity signaling has been shown to be involved in the posterior positioning of the basal bodies of nodal cilia, which leads to the posterior tilting of their rotation axes. Second, identification of putative receptors and signaling molecules suggests a link between the signaling molecules delivered by the nodal flow, and downstream signaling in the cells surrounding the nodal cavity and the lateral plate mesoderm.

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Quantitative analysis of gradient sensing: towards building predictive models of chemotaxis in cancer.

Publication Date: 2012 Jan 25 PMID: 22284347
Authors: Hughes-Alford, S. K. - Lauffenburger, D. A.
Journal: Curr Opin Cell Biol

Chemotaxis of tumor cells in response to a gradient of extracellular ligand is an important step in cancer metastasis. The heterogeneity of chemotactic responses in cancer has not been widely addressed by experimental or mathematical modeling techniques. However, recent advancements in chemoattractant presentation, fluorescent-based signaling probes, and phenotypic analysis paradigms provide rich sources for building data-driven relational models that describe tumor cell chemotaxis in response to a wide variety of stimuli. Here we present gradient sensing, and the resulting chemotactic behavior, in a 'cue-signal-response' framework and suggest methods for utilizing recently reported experimental methods in data-driven modeling ventures.

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An Intracellular Transmission Control Protocol: assembly and transport of ribonucleoprotein complexes.

Publication Date: 2012 Jan 23 PMID: 22278045
Authors: Marchand, V. - Gaspar, I. - Ephrussi, A.
Journal: Curr Opin Cell Biol

Initially assumed to be a special feature of highly polarized eukaryotic cells, recent evidence suggests that mRNA localization coupled with local translation is a widespread strategy for spatial restriction of protein synthesis within cells. Genome-wide analyses and live imaging approaches have shed new light on the prevalence and the mechanistic details of this phenomenon. Here we review some of the recent findings that have emerged from research from the RNA localization field, from the birth of mRNAs in the nucleus, to their delivery at specific sites within the cytoplasm.

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Integration of morphogen signalling within the growth regulatory network.

Publication Date: 2012 Jan 16 PMID: 22257639
Authors: Baena-Lopez, L. A. - Nojima, H. - Vincent, J. P.
Journal: Curr Opin Cell Biol

The need to coordinate patterning and growth has been appreciated for many years. The logic that enables seamless integration of the relevant inputs is beginning to be elucidated, particularly in wing imaginal discs of Drosophila. In this tissue, multiple regulatory layers involving the two morphogens Wingless and Dpp, the wing-specific determinant, Vestigial, and the Hippo pathway, converge to regulate growth. Intricate cross-regulation between these components may explain why, at the local level, there is no direct correlation between growth and the graded signalling activity of Wingless and Dpp, despite the requirement of these two pathways for growth.

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Pattern formation in centrosome assembly.

Publication Date: 2012 Jan 13 PMID: 22245706
Authors: Mahen, R. - Venkitaraman, A. R.
Journal: Curr Opin Cell Biol

A striking but poorly explained feature of cell division is the ability to assemble and maintain organelles not bounded by membranes, from freely diffusing components in the cytosol. This process is driven by information transfer across biological scales such that interactions at the molecular scale allow pattern formation at the scale of the organelle. One important example of such an organelle is the centrosome, which is the main microtubule organising centre in the cell. Centrosomes consist of two centrioles surrounded by a cloud of proteins termed the pericentriolar material (PCM). Profound structural and proteomic transitions occur in the centrosome during specific cell cycle stages, underlying events such as centrosome maturation during mitosis, in which the PCM increases in size and microtubule nucleating capacity. Here we use recent insights into the spatio-temporal behaviour of key regulators of centrosomal maturation, including Polo-like kinase 1, CDK5RAP2 and Aurora-A, to propose a model for the assembly and maintenance of the PCM through the mobility and local interactions of its constituent proteins. We argue that PCM structure emerges as a pattern from decentralised self-organisation through a reaction-diffusion mechanism, with or without an underlying template, rather than being assembled from a central structural template alone. Self-organisation of this kind may have broad implications for the maintenance of mitotic structures, which, like the centrosome, exist stably as supramolecular assemblies on the micron scale, based on molecular interactions at the nanometer scale.

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3D ultrastructure of the nuclear pore complex.

Publication Date: 2012 Jan 11 PMID: 22244612
Authors: Bilokapic, S. - Schwartz, T. U.
Journal: Curr Opin Cell Biol

Nuclear pore complexes (NPCs) perforate the double-layered nuclear envelope and form the main gateway for molecular exchange between nucleus and cytoplasm of the eukaryotic cell. Because NPCs are extraordinarily complex and large, thus challenging to investigate on a molecular level, they are still rather poorly understood, despite their pivotal role in cellular homeostasis. To decipher the NPC structure at high resolution, the prerequisite to fully understand its function, a tailored approach is necessary that feeds from complimentary data, obtained at largely different spatial resolutions. The problem is further complicated by the dynamic nature of the NPC, manifested in flexible regions and dynamic components. Here we summarize the current state of these structural efforts, describe the breakthroughs of recent years, point out the existing disputes in the field, and give an outlook of what we should expect to happen in the near future.

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Structure, function and dynamics of nuclear subcompartments.

Publication Date: 2012 Jan 5 PMID: 22227228
Authors: Cardoso, M. C. - Schneider, K. - Martin, R. M. - Leonhardt, H.
Journal: Curr Opin Cell Biol

The nucleus contains a plethora of different dynamic structures involved in the regulation and catalysis of nucleic acid metabolism and function. Over the past decades countless factors, molecular structures, interactions and posttranslational modifications have been described in this context. On the one side of the size scale X-ray crystallography delivers static snapshots of biomolecules at atomic resolution and on the other side light microscopy allows insights into complex structures of living cells and tissues in real time but poor resolution. Recent advances in light and electron microscopy are starting to close the temporal and spatial resolution gap from the atomic up to the cellular level. Old challenges and new insights are illustrated with examples of DNA replication and nuclear protein dynamics.

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The role of mobile small RNA species during root growth and development.

Publication Date: 2012 Jan 5 PMID: 22227227
Authors: Furuta, K. - Lichtenberger, R. - Helariutta, Y.
Journal: Curr Opin Cell Biol

In animals and plants, small RNAs have been identified as important regulatory factors controlling cell fate. A bidirectional cell-to-cell communication involving the mobile transcription factor SHR and microRNA165/166 species specifies the radial position of two types of xylem vessels in Arabidopsis roots. The microRNAs provide short-range non-cell-autonomous developmental signals that are transported through the plasmodesmata (PD) via the symplastic pathway. 21-24 nucleotide-long small RNA species have been shown to move from the shoot to the root. In this review, we highlight the presence of small RNA species as an emerging class of important mobile signals associated with the growth and development of the root.

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