Understanding the influence of substrate when growing tumorspheres

Background Cancer stem cells are important for the development of many solid tumors. These cells receive promoting and inhibitory signals that depend on the nature of their environment (their niche) and determine cell dynamics. Mechanical stresses are crucial to the initiation and interpretation of these signals. Methods A two-population mathematical model of tumorsphere growth is used to interpret the results of a series of experiments recently carried out in Tianjin, China, and extract information about the intraspecific and interspecific interactions between cancer stem cell and differentiated cancer cell populations. Results The model allows us to reconstruct the time evolution of the cancer stem cell fraction, which was not directly measured. We find that, in the presence of stem cell growth factors, the interspecific cooperation between cancer stem cells and differentiated cancer cells induces a positive feedback loop that determines growth, independently of substrate hardness. In a frustrated attempt to reconstitute the stem cell niche, the number of cancer stem cells increases continuously with a reproduction rate that is enhanced by a hard substrate. For growth on soft agar, intraspecific interactions are always inhibitory, but on hard agar the interactions between stem cells are collaborative while those between differentiated cells are strongly inhibitory. Evidence also suggests that a hard substrate brings about a large fraction of asymmetric stem cell divisions. In the absence of stem cell growth factors, the barrier to differentiation is broken and overall growth is faster, even if the stem cell number is conserved. Conclusions Our interpretation of the experimental results validates the centrality of the concept of stem cell niche when tumor growth is fueled by cancer stem cells. Niche memory is found to be responsible for the characteristic population dynamics observed in tumorspheres. The model also shows why substratum stiffness has a deep influence on the behavior of cancer stem cells, stiffer substrates leading to a larger proportion of asymmetric doublings. A specific condition for the growth of the cancer stem cell number is also obtained

Artificial Reef Monitoring Structures (ARMS) providing insights on hard substrate biodiversity and community structure of the Eastern Mediterranean Sea

Monitoring marine biodiversity in hard-bottom habitats is challenging as it typically involves resource-intensive, non-standardized, and often destructive sampling methods that limit its scalability. Differences in monitoring approaches furthermore hinder inter-comparison among monitoring programs. Standardised collectors such as Artificial Reef Monitoring Structures (ARMS) can be used to monitor status and changes of hard substrate communities in coastal environments. In addition, ARMS constitute an early-warning system for marine biological invasions by identifying newly introduced Non-Indigenous Species (NIS) and track the migration patterns of already known NIS in European continental waters. In the framework of ASSEMBLE+ project and as part of the European ARMS programme (ARMS-MBON) (Obst et al. 2020), ARMS were deployed in two locations in Greece and, more specifically, in the marina of the Old Venetian Harbour of Heraklion (1HERP) and in the Underwater Biotechnological Park of the Hellenic Centre for Marine Research (2UBPC). The ARMS deployment and retrieval dates are shown in Table 1; deployment and retrieval were done according to the standards and protocols established by the Smithsonian Institution. Upon retrieval, the plates from the ARMS were disassembled, photographed (Fig. 1a) and samples of both the motile and sessile communities were collected for molecular analysis. Each sampling event produced three fractions (sessile, motile 90–500 μm and motile 500 μm−2 mm) as well as a stack of plate and specimen images. DNA was extracted from the sampled fractions and amplified by PCR, targeting different molecular markers (18S rRNA, COI and ITS). Resulting amplicons were sequenced using Illumina MiSeq Reagent Kit v3 (2 × 300 bp) and analyzed using PEMA (Zafeiropoulos et al. 2020). All raw sequence files of this study were submitted to the European Nucleotide Archive (ENA) (Harrison et al. 2021) with the study accession number PRJEB33796. Images were analyzed using photoQuad image processing software (Trygonis and Sini 2012), which is specialised for the analysis of sessile biodiversity on photoquadrats. Cover of sessile taxa was measured by superimposing on every image 100 randomly distributed points. Each point was manually assigned to the corresponding taxon or morpho-functional category based on external morphological characters. Repeatable workflow procedures for integrated processing of image and sequence data are currently under development as part of the LifeWatch-ERIC Internal Joint Initiative on NIS. In addition, all ARMS-related data are stored in the ASSEMBLE Plus data collection of the Marine Data Archive (MDA) using a Darwin Core Archive (DwC-A) format, including the linkages to the images and sequences (Exter et al. 2020). Comparison of traditional biodiversity assessment methods, such as image-based identifications, complemented by the eDNA metabarcoding results, will shed light on the investigation of marine biodiversity patterns in the Eastern Mediterranean Sea (Fig. 1b). Furthermore, the results will provide crucial information on the importance of ARMS for biodiversity assessment and as an efficient tool to monitor community shifts and invasion events in marine ecosystems undegoing fast change.

EARLY–MIDDLE ORDOVICIAN SEASCAPE-SCALE AGGREGATION PATTERN OF SPONGE-RICH REEFS ACROSS THE LAURENTIA PALEOCONTINENT

ABSTRACT During the late Cambrian–Early Ordovician interval the predominant non-microbial reef builders were sponges or sponge-like metazoans. The lithological and faunal composition of Cambro-Ordovician sponge-dominated reefs have previously been analyzed and reviewed. Here we take the relationship between reef aggregation pattern at reef to seascape scale into account, and look for changes during the Early–Middle Ordovician interval, in which metazoans became dominant reef builders. In a comparison of sponge-rich reefs from eight sites of the Laurentia paleocontinent three different seascape level reef growth patterns can be distinguished: (1) mosaic mode of reef growth, where reefs form a complex spatial mosaic dependent on hard substrate; (2) episodic mode, where patch reefs grew exclusively in distinct unconformity bounded horizons within non-reefal lithological units that have a much larger thickness; and (3) belt-and-bank mode, where reefs and reef complexes grew vertically and laterally as dispersed patches largely independent from truncation surfaces. The distinct modes of growth likely represent specific reef forming paleocommunities, because they differ in content and abundance of skeletal metazoan framebuilders, bioturbation intensity of non-skeletal reef sediment matrix, and in association of reef growth with underlying hard substrate. We suggest, based on a review of Laurentian reef occurrences, that the mosaic mode dominated in Early Ordovician strata and that the dominance shifted toward the belt and bank mode from Middle Ordovician strata onward.