Cancer Stem Cells and Their Vesicles, Together with Other Stem and Non-Stem Cells, Govern Critical Cancer Processes: Perspectives for Medical Development

Stem cells, identified several decades ago, started to attract interest at the end of the nineties when families of mesenchymal stem cells (MSCs), concentrated in the stroma of most organs, were found to participate in the therapy of many diseases. In cancer, however, stem cells of high importance are specific to another family, the cancer stem cells (CSCs). This comprehensive review is focused on the role and the mechanisms of CSCs and of their specific extracellular vesicles (EVs), which are composed of both exosomes and ectosomes. Compared to non-stem (normal) cancer cells, CSCs exist in small populations that are preferentially distributed to the niches, such as minor specific tissue sites corresponding to the stroma of non-cancer tissues. At niches and marginal sites of other cancer masses, the tissue exhibits peculiar properties that are typical of the tumor microenvironment (TME) of cancers. The extracellular matrix (ECM) includes components different from non-cancer tissues. CSCs and their EVs, in addition to effects analogous to those of MSCs/EVs, participate in processes of key importance, specific to cancer: generation of distinct cell subtypes, proliferation, differentiation, progression, formation of metastases, immune and therapy resistance, cancer relapse. Many of these, and other, effects require CSC cooperation with surrounding cells, especially MSCs. Filtered non-cancer cells, especially macrophages and fibroblasts, contribute to collaborative cancer transition/integration processes. Therapy developments are mentioned as ongoing preclinical initiatives. The preliminary state of clinical medicine is presented in terms of both industrial development and future treatments. The latter will be administered to specific patients together with known drugs, with the aim of eradicating their tumor growth and metastases.

Spatiotemporal Variations in Seed Set and Pollen Limitation in Populations of the Rare Generalist Species Polemonium caeruleum in Poland

A vast majority of angiosperms are pollinated by animals, and a decline in the number and diversity of insects often affects plant reproduction through pollen limitation. This phenomenon may be particularly severe in rare plant species, whose populations are shrinking. Here, we examined the variability in factors shaping reproductive success and pollen limitation in red-listed Polemonium caeruleum L. During a 5-year study in several populations of P. caeruleum (7–15, depending on year), we assessed the degree of pollen limitation based on differences in seed set between open-pollinated (control) and hand-pollinated flowers. We analysed the effects of flower visitors, population size, and meteorological data on plant reproductive success and pollen limitation. Our study showed that pollen limitation rarely affected P. caeruleum populations, and was present mainly in small populations. Pollen limitation index was negatively affected by the size of population, visitation frequency of all insects, and when considering the visitation frequency of individual groups, also by honeybee visits. Seed production in control treatment was positively influenced by the population size, average monthly precipitation in June and visits of hoverflies, while visits of honeybees, average monthly temperature in September, and average monthly precipitation in August influenced seed production negatively. As generalist plant P. caeruleum can be pollinated by diverse insect groups, however, in small populations their main visitors, the honeybees and bumblebees, may be less attracted, eventually leading to the disappearance of these populations. In pollination of P. caeruleum managed honeybees may play a dual role: while they are the most frequent and efficient flower visitors, their presence decreases seed set in open-pollinated flowers, which is most probably related to efficient pollen collection by these insects.

The costs and benefits of dispersal in small populations

Dispersal has three major effects on adaptation. First, the gene flow mixes alleles adapted to different environments, potentially hindering (swamping) adaptation. Second, it inflates genetic variance: this aids adaptation to spatially (and temporally) varying environments but if selection is hard, it lowers the mean fitness of the population. Third, neighbourhood size, which determines how weak genetic drift is, increases with dispersal -- when genetic drift is strong, increase of neighbourhood size with dispersal aids adaptation. In this note I focus on the role of dispersal in environments which change smoothly across space, and when local populations are quite small such that genetic drift has a significant effect. Using individual-based simulations, I show that in small populations, even leptokurtic dispersal benefits adaptation, by reducing the power of genetic drift. This has implications for management of small marginal populations: increased gene flow appears beneficial as long as adaptations involves a quantitative, rather than a discrete, trait. However, heavily leptokurtic dispersal will swamp continuous adaptation along steep environmental gradients so that only patches of locally adapted subpopulations remain.

Population size impacts host–pathogen coevolution

Ongoing host–pathogen interactions are characterized by rapid coevolutionary changes forcing species to continuously adapt to each other. The interacting species are often defined by finite population sizes. In theory, finite population size limits genetic diversity and compromises the efficiency of selection owing to genetic drift, in turn constraining any rapid coevolutionary responses. To date, however, experimental evidence for such constraints is scarce. The aim of our study was to assess to what extent population size influences the dynamics of host–pathogen coevolution. We used Caenorhabditus elegans and its pathogen Bacillus thuringiensis as a model for experimental coevolution in small and large host populations, as well as in host populations which were periodically forced through a bottleneck. By carefully controlling host population size for 23 host generations, we found that host adaptation was constrained in small populations and to a lesser extent in the bottlenecked populations. As a result, coevolution in large and small populations gave rise to different selection dynamics and produced different patterns of host–pathogen genotype-by-genotype interactions. Our results demonstrate a major influence of host population size on the ability of the antagonists to co-adapt to each other, thereby shaping the dynamics of antagonistic coevolution.

River network rearrangements promote speciation in lowland Amazonian birds

Large Amazonian rivers impede dispersal for many species, but lowland river networks frequently rearrange, thereby altering the location and effectiveness of river-barriers through time. These rearrangements may promote biotic diversification by facilitating episodic allopatry and secondary contact among populations. We sequenced genome-wide markers to evaluate histories of divergence and introgression in six Amazonian avian species-complexes. We first tested the assumption that rivers are barriers for these taxa and found that even relatively small rivers facilitate divergence. We then tested whether species diverged with gene flow and recovered reticulate histories for all species, including one potential case of hybrid speciation. Our results support the hypothesis that river dynamics promote speciation and reveal that many rainforest taxa are micro-endemic, unrecognized and thus threatened with imminent extinction. We propose that Amazonian hyper-diversity originates in part from fine-scale barrier displacement processes, including river dynamics, which allow small populations to differentiate and disperse into secondary contact.

The Use of Genomic Information for the Conservation of Animal Genetic Diversity

The conservation of genetic diversity, both among and within breeds, is a costly process. Therefore, choices between breeds and animals within breeds are unavoidable, either for conservation in vitro (gene banks) or in vivo (maintaining small populations alive). Nowadays, genomic information on breeds and individual animals is the standard for the choices to be made in conservation. Genomics may accurately measure the genetic distances among breeds and the relationships among animals within breeds. Homozygosity at loci and at parts of chromosomes is used to measure inbreeding. In addition, genomics can be used to detect potentially valuable rare alleles and haplotypes, their carriers in these breeds and can facilitate in vivo or in vitro conservations of these genomic regions.

Distinct Genetic Structure Reflects Ploidy Level Differentiation in Newly Discovered, Extremely Small Populations of Xanthocyparis vietnamensis from Southwestern China

Population genetic assessment is crucial for the conservation and management of threatened species. Xanthocyparis vietnamensis is an endangered species that is currently restricted to karst mountains in southwestern China and Vietnam. This rare conifer was first recorded in 2002 from northern Vietnam and then in 2013 from Guangxi, China, yet nothing is known about its genetic diversity nor ploidy level variation, although previous cytological study suggest that Vietnamese populations are tetraploids. There have been about 45 individuals found to date in Guangxi, China. Here, we genotyped 33 X. vietnamensis individuals using 20 newly developed, polymorphic microsatellite loci, to assess the genetic variability of its extremely small populations. The genetic diversity of X. vietnamensis (HE = 0.511) was lower than that of two other heliophile species, Calocedrus macrolepis and Fokienia hodginsii, which have similar distribution ranges. This is consistent with the signature of a genetic bottleneck detected in X. vietnamensis. Although the population genetic differentiation coefficient across loci is moderate (FST = 0.125), STRUCTURE analysis revealed two distinct genetic clusters, namely the northern and southern population groups; DAPC analysis grouped the southern populations together in one cluster separate from the northern populations; AMOVA analysis detected a significant genetic differentiation between the two population groups (FRT = 0.089, p < 0.05), and BARRIER analysis detected a genetic barrier between them. Moreover, we detected differentiation in ploidy level between northern and southern populations, sampled individuals from the former and the later are all diploid and tetraploid cytotypes with mean genome sizes of 26.08 and 48.02 pg/2C, respectively. We deduced that heterogeneous geomorphology and historical events (e.g., human deforestation, Quaternary climate oscillations) may have contributed to population fragmentation and small population size in X. vietnamensis. Considering both genetic and ploidy level differentiation, we propose that two different management units (northern and southern) should be considered and a combination of in situ and ex situ conservation measures should be employed to preserve populations of this endangered species in southwestern China in the light of our findings.

Lagenophora schmidiae (Asteraceae), a critically threatened new species from Aotearoa / New Zealand

Lagenophora schmidiae de Lange & Jian Wang ter sp. nov. (Asteraceae) is described, illustrated and differentiated from L. montana Hook.f. The new species was first recorded from Aotearoa / New Zealand in 1974, when it was identified as L. montana. This relatively recent recognition reflects in part the fact that the new species is extremely uncommon, and has often been confused with the superficially similar L. barkeri Kirk, with which it often grows. A conservation status for L. schmidiae of ‘Threatened / Nationally Critical’ using the New Zealand Threat Classification System is proposed, as the new species is known only from small populations, many of which are threatened by alien weed invasion.

Begonia pseudoedulis, a new species in Begonia sect. Platycentrum (Begoniaceae) from southern Guangxi of China

Begonia pseudoedulis, a new species in Begonia sect. Platycentrum (Klotzsch) A.DC. (Begoniaceae) from southern Guangxi of China, is here described and illustrated. It morphologically resembles B. edulis H.Lév. and B. dielsiana E.Pritz. ex Diels but differs easily by its hairy petioles and inflorescences, and red hispidulous flower tepals, ovary and capsules. The molecular phylogenetic analysis based on ITS supported that the new species was a monophyletic lineage, separating from both B. dielsiana and B. edulis. Due to its isolated distribution with several small populations, which are possibly disturbed by human activities, the species is considered as “Near Threatened” (NT) according to the IUCN Red List Categories and Criteria.