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Contains fulltext : 250997.pdf (Publisher’s version ) (Closed access)

Contains fulltext : 250997.pdf (Publisher’s version ) (Closed access)

Contains fulltext : 250997.pdf (Publisher’s version ) (Closed access)

Contains fulltext : 250997.pdf (Publisher’s version ) (Closed access)

Contains fulltext : 250997.pdf (Publisher’s version ) (Closed access)

Human cholangiocyte organoids show great promise for regenerative therapies and in vitro modeling of bile duct development and diseases. However, the cystic organoids lack the branching morphology of intrahepatic bile ducts (IHBDs). Here, we report establishing human branching cholangiocyte organoid (BRCO) cultures. BRCOs self-organize into complex tubular structures resembling the IHBD architecture. Single-cell transcriptomics and functional analysis showed high similarity to primary cholangiocytes, and importantly, the branching growth mimics aspects of tubular development and is dependent on JAG1/NOTCH2 signaling. When applied to cholangiocarcinoma tumor organoids, the morphology changes to an in vitro morphology like primary tumors. Moreover, these branching cholangiocarcinoma organoids (BRCCAOs) better match the transcriptomic profile of primary tumors and showed increased chemoresistance to gemcitabine and cisplatin. In conclusion, BRCOs recapitulate a complex process of branching morphogenesis in vitro. This provides an improved model to study tubular formation, bile duct functionality, and associated biliary diseases.

Although melanoma is notorious for its high degree of heterogeneity and plasticity1,2, the origin and magnitude of cell-state diversity remains poorly understood. Equally, it is unclear whether growth and metastatic dissemination are supported by overlapping or distinct melanoma subpopulations. Here, by combining mouse genetics, single-cell and spatial transcriptomics, lineage tracing and quantitative modelling, we provide evidence of a hierarchical model of tumour growth that mirrors the cellular and molecular logic underlying the cell-fate specification and differentiation of the embryonic neural crest. We show that tumorigenic competence is associated with a spatially localized perivascular niche, a phenotype acquired through an intercellular communication pathway established by endothelial cells. Consistent with a model in which only a fraction of cells are fated to fuel growth, temporal single-cell tracing of a population of melanoma cells with a mesenchymal-like state revealed that these cells do not contribute to primary tumour growth but, instead, constitute a pool of metastatic initiating cells that switch cell identity while disseminating to secondary organs. Our data provide a spatially and temporally resolved map of the diversity and trajectories of melanoma cell states and suggest that the ability to support growth and metastasis are limited to distinct pools of cells. The observation that these phenotypic competencies can be dynamically acquired after exposure to specific niche signals warrant the development of therapeutic strategies that interfere with the cancer cell reprogramming activity of such microenvironmental cues., SCOPUS: ar.j, info:eu-repo/semantics/published

Patches of vegetation consist of dense clusters of shrubs, grass, or trees, often found to be circular characteristic size, defined by the properties of the vegetation and terrain. Therefore, vegetation patches can be interpreted as localized structures. Previous findings have shown that such localized structures can self-replicate in a binary fashion, where a single vegetation patch elongates and divides into two new patches, in a process resembling cellular mitosis. Here, we extend these previous results by considering the more general case, where the plants interact non-locally, this extension adds an extra level of complexity and shrinks the gap between the model and real ecosystems, where it is known that the plant-to-plant competition through roots and above-ground facilitating interactions have non-local effects, i.e. they extend further away than the nearest neighbor distance. Through numerical simulations, we show that for a moderate level of aridity, a transition from a single patch to periodic pattern occurs. Moreover, for large values of the hydric stress, we predict an opposing route to the formation of periodic patterns, where a homogeneous cover of vegetation may decay to spot-like patterns. The evolution of the biomass of vegetation patches can be used as an indicator of the state of an ecosystem, allowing to distinguish if a system is in a self-replicating or decaying dynamics. In an attempt to relate the theoretical predictions to real ecosystems, we analyze landscapes in Zambia and Mozambique, where vegetation forms patches of tens of meters in diameter. We show that the properties of the patches together with their spatial distributions are consistent with the self-organization hypothesis. We argue that the characteristics of the observed landscapes may be a consequence of patch self-replication, however, detailed field and temporal data is fundamental to assess the real state of the ecosystems., SCOPUS: ar.j, info:eu-repo/semantics/published

Desertification due to climate change and increasing drought periods is a worldwide problem for both ecology and economy. Our ability to understand how vegetation manages to survive and propagate through arid and semiarid ecosystems may be useful in the development of future strategies to prevent desertification, preserve flora-and fauna within-or even make use of scarce resources soils. In this paper, we study a robust phenomena observed in semi-arid ecosystems, by which localized vegetation patches split in a process called self-replication. Localized patches of vegetation are visible in nature at various spatial scales. Even though they have been described in literature, their growth mechanisms remain largely unexplored. Here, we develop an innovative statistical analysis based on real field observations to show that patches may exhibit deformation and splitting. This growth mechanism is opposite to the desertification since it allows to repopulate territories devoid of vegetation. We investigate these aspects by characterizing quantitatively, with a simple mathematical model, a new class of instabilities that lead to the self-replication phenomenon observed., SCOPUS: ar.j, info:eu-repo/semantics/published

Desertification due to climate change and increasing drought periods is a worldwide problem for both ecology and economy. Our ability to understand how vegetation manages to survive and propagate through arid and semiarid ecosystems may be useful in the development of future strategies to prevent desertification, preserve flora-and fauna within-or even make use of scarce resources soils. In this paper, we study a robust phenomena observed in semi-arid ecosystems, by which localized vegetation patches split in a process called self-replication. Localized patches of vegetation are visible in nature at various spatial scales. Even though they have been described in literature, their growth mechanisms remain largely unexplored. Here, we develop an innovative statistical analysis based on real field observations to show that patches may exhibit deformation and splitting. This growth mechanism is opposite to the desertification since it allows to repopulate territories devoid of vegetation. We investigate these aspects by characterizing quantitatively, with a simple mathematical model, a new class of instabilities that lead to the self-replication phenomenon observed., SCOPUS: ar.j, info:eu-repo/semantics/published

info:eu-repo/semantics/published

The stability of a circular localized spot with respect to azimuthal perturbations is studied in a prototype variational model, namely, a Swift-Hohenberg type equation. The conditions under which the circular shape of the spot undergoes an elliptical deformation which transforms it into a rod-shaped structure are analyzed. As it elongates, the rod structure exhibits a transversal instability, generating an invaginated labyrinthine structure which invades all the space available., SCOPUS: ar.j, info:eu-repo/semantics/published