Like most bilaterian animals, the annelid Platynereis dumerilii generates the majority of its body axis in an anterior to posterior temporal progression with new segments added sequentially. This process relies on a posterior subterminal proliferative body region, known as the "segment addition zone" (SAZ). We explored some of the molecular and cellular aspects of posterior elongation in Platynereis, in particular to test the hypothesis that the SAZ contains a specific set of stem cells dedicated to posterior elongation. We cloned and characterized the developmental expression patterns of orthologs of 17 genes known to be involved in the formation, behavior, or maintenance of stem cells in other metazoan models. These genes encode RNA-binding proteins (e.g., tudor, musashi, pumilio) or transcription factors (e.g., myc, id, runx) widely conserved in eumetazoans. Most of these genes are expressed both in the migrating primordial germ cells and in overlapping ring-like patterns in the SAZ, similar to some previously analyzed genes (piwi, vasa). The SAZ patterns are coincident with the expression of proliferation markers cyclin B and PCNA. EdU pulse and chase experiments suggest that new segments are produced through many rounds of divisions from small populations of teloblast-like posterior stem cells. The shared molecular signature between primordial germ cells and posterior stem cells in Platynereis thus corresponds to an ancestral "stemness" program.

Despite the tight historical links between science and philosophy, hearkening back to Plato, Aristotle, and others (here evoked with Raphael's famous School of Athens), present-day scientists often perceive philosophy as completely different from, and even antagonistic to, science. To the contrary, we believe philosophy can have an important and productive impact on science. Image credit: Shutterstock.com/Isogood_patrick. a Institut d'histoire et de philosophie des sciences et des techniques (UMR8590),

The notion of tumor microenvironment (TME) has been brought to the forefront of recent scientific literature on cancer. However, there is no consensus on how to define and spatially delineate the TME. We propose that time is ripe to go beyond an all-encompassing list of the components of the TME, and to construct a multi-layered view of cancer. We distinguish six layers of environmental interactions with the tumor, and show that they are associated with distinct mechanisms, and ultimately with distinct therapeutic approaches.

In contrast to the once dominant tumour‐centric view of cancer, increasing attention is now being paid to the tumour microenvironment (TME), generally understood as the elements spatially located in the vicinity of the tumour. Thinking in terms of TME has proven extremely useful, in particular because it has helped identify and comprehend the role of nongenetic and noncell‐intrinsic factors in cancer development. Yet some current approaches have led to a TME‐centric view, which is no less problematic than the former tumour‐centric vision of cancer, insofar as it tends to overlook the role of components located beyond the TME, in the ‘tumour organismal environment’ (TOE). In this minireview, we highlight the explanatory and therapeutic shortcomings of the TME‐centric view and insist on the crucial importance of the TOE in cancer progression.

The characteristic properties of stem cells – notably their ability to self-renew and to differentiate – have meant that they have traditionally been viewed as distinct from most other types of cells. However, recent research has blurred the line between stem cells and other cells by showing that the former display a range of behaviors in different tissues and at different stages of development. Here, we use the tools of metaphysics to describe a classification scheme for stem cells, and to highlight what their inherent diversity means for cancer treatment.

Mouse models of chronic myeloid malignancies suggest that targeting mature cells of the malignant clone disrupts feedback loops that promote disease expansion. Here, we show that, in chronic myelomonocytic leukemia (CMML), monocytes that accumulate in the peripheral blood show a decreased propensity to die by apoptosis. BH3 profiling demonstrates their addiction to MCL1 (myeloid cell leukemia-1), which can be targeted with the small molecule inhibitor S63845. RNA sequencing and DNA methylation pattern analysis both point also to the implication of the MAPK (mitogen-activated protein kinase) pathway in the resistance of CMML monocytes to death and reveal an autocrine pathway in which the secreted cytokine CYTL1 (Cytokine-like protein 1) promotes ERK (extracellular signal-regulated kinase) activation through CCR2 (C-C chemokine receptor type 2). Combined MAPK and MCL1 inhibition restores apoptosis of CMML patient monocytes and reduces the expansion of patient-derived xenografts in mice. These results designate the combined inhibition of MCL1 and MAPK as a promising approach to slow down CMML progression by inducing leukemic monocyte apoptosis.

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Similar to seemingly maladaptive genes in general, the persistence of inherited cancer-causing mutant alleles in populations remains a challenging question for evolutionary biologists. In addition to traditional explanations such as senescence or antagonistic pleiotropy, here we put forward a new hypothesis to explain the retention of oncogenic mutations. We propose that although natural defenses evolve to prevent neoplasm formation and progression thus increasing organismal fitness, they also conceal the effects of cancer-causing mutant alleles on fitness and concomitantly protect inherited ones from purging by purifying selection. We also argue for the importance of the ecological contexts experienced by individuals and/or species. These contexts determine the locally predominant fitness-reducing risks, and hence can aid the prediction of how natural selection will influence cancer outcomes.