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The maintenance of B cell identity requires active transcriptional control that enforces a B cell–specific program and suppresses alternative lineage genes. Accordingly, disrupting the B cell identity regulatory network compromises B cell function and induces cell fate plasticity by allowing derepression of alternative lineage-specific transcriptional programs. Although the B lineage is incredibly resistant to most differentiating factors, loss of just a single B lineage–specific transcription factor or the forced expression of individual non–B cell lineage transcription factors can radically disrupt B cell maintenance and allow dedifferentiation or transdifferentiation into entirely distinct lineages. B lymphocytes thereby offer an insightful and useful case study of how a specific cell lineage can maintain a stable identity throughout life and how perturbations of a single master regulator can induce cellular plasticity. In this article, we review the regulatory mechanisms that safeguard B cell identity, and we discuss how dysregulation of the B cell maintenance program can drive malignant transformation and enable therapeutic resistance.

Changes in behaviour may initiate shifts to new adaptive zones, with physical adaptations for novel environments evolving later. While new mutations are commonly considered engines of adaptive change, sensory evolution enabling access to new resources might also arise from standing genetic diversity, and even gene loss. We examine the relative contribution of molecular adaptations, measured by positive and relaxed selection, acting on eye-expressed genes associated with shifts to new adaptive zones in ecologically diverse bats from the superfamily Noctilionoidea. Collectively, noctilionoids display remarkable ecological breadth, from highly divergent echolocation to flight strategies linked to specialized insectivory, the parallel evolution of diverse plant-based diets (e.g., nectar, pollen and fruit) from ancestral insectivory, and-unusually for echolocating bats-often have large, well-developed eyes. We report contrasting levels of positive selection in genes associated with the development, maintenance and scope of visual function, tracing back to the origins of noctilionoids and Phyllostomidae (the bat family with most dietary diversity), instead of during shifts to novel diets. Generalized plant visiting was not associated with exceptional molecular adaptation, and exploration of these novel niches took place in an ancestral phyllostomid genetic background. In contrast, evidence for positive selection in vision genes was found at subsequent shifts to either nectarivory or frugivory. Thus, neotropical noctilionoids that use visual cues for identifying food and roosts, as well as for orientation, were effectively preadapted, with subsequent molecular adaptations in nectar-feeding lineages and the subfamily Stenodermatinae of fig-eating bats fine-tuning pre-existing visual adaptations for specialized purposes.

Our modern era is witnessing an increasing infertility rate worldwide. Although some of the causes can be attributed to our modern lifestyle (e.g., persistent organic pollutants, late pregnancy), our knowledge of the human ovarian tissue has remained limited and insufficient to reverse the infertility statistics. Indeed, all efforts have been focused on the endocrine and cellular function in support of the cell theory that dates back to the 18th century, while the human ovarian matrisome is still under-described. Hereby, we unveil the extracellular side of the story during different periods of the ovary life, demonstrating that follicle survival and development, and ultimately fertility, would not be possible without its involvement. We examined the human ovarian matrisome and described its remodeling from prepuberty until menopause, creating the first ovarian proteomic codex. Here, we confidently identified and quantified 98 matrisome proteins present in the three ovary groups. Among them, 26 were expressed differently among age groups, delineating a peculiar matrisomal fingerprint at each stage. Such proteins could be potential biomarkers phenotyping ovarian ECM at each age phase of female reproductive life. Beyond proteomics, our study presents a unique approach to understanding the data and depicting the spatiotemporal ECM-intracellular signaling networks and remodeling with age through imaging, advanced text-mining based on natural language processing technology, machine learning, and data sonification. Our findings provide essential context for healthy ovarian physiology, identifying and characterizing disease states, and recapitulating physiological tissues or development in vitro. This comprehensive proteomics analysis represents the ovarian proteomic codex and contributes to an improved understanding of the critical roles that ECM plays throughout the ovarian life span.

Significance A cell must be able to measure whether the lipid membranes that surround its insides are stretched. Currently, mechanosensitive ion channels are the best-studied class of membrane tension sensors, but recent work suggests that peripheral membrane enzymes that gauge nuclear confinement or swelling during cell migration or upon tissue injury constitute a second class. The mechanosensitivity of these enzymes derives from their calcium-dependent (“C2-like”) membrane-interaction domains. Although these can be found in many important signaling proteins, they have remained virtually unstudied as mechanotransducers. How membrane tension controls these domains and what features render them mechanosensitive is unclear. Here, we show that membrane tension-sensing by C2-like domains is mediated by a synergy between mechanosensitive calcium-binding and membrane insertion., When nuclear membranes are stretched, the peripheral membrane enzyme cytosolic phospholipase A2 (cPLA2) binds via its calcium-dependent C2 domain (cPLA2-C2) and initiates bioactive lipid signaling and tissue inflammation. More than 150 C2-like domains are encoded in vertebrate genomes. How many of them are mechanosensors and quantitative relationships between tension and membrane recruitment remain unexplored, leaving a knowledge gap in the mechanotransduction field. In this study, we imaged the mechanosensitive adsorption of cPLA2 and its C2 domain to nuclear membranes and artificial lipid bilayers, comparing it to related C2-like motifs. Stretch increased the Ca2+ sensitivity of all tested domains, promoting half-maximal binding of cPLA2 at cytoplasmic resting-Ca2+ concentrations. cPLA2-C2 bound up to 50 times tighter to stretched than to unstretched membranes. Our data suggest that a synergy of mechanosensitive Ca2+ interactions and deep, hydrophobic membrane insertion enables cPLA2-C2 to detect stretched membranes with antibody-like affinity, providing a quantitative basis for understanding mechanotransduction by C2-like domains.

International audience; The survival of our civilization is entirely dependent on plants. Nevertheless, many relevant aspects of plant biology remain unknown. One of the most intriguing is the biological process of plant growth and morphogenesis. The conundrum of plant growth lies in the rigid polysaccharide network surrounding every plant cell: the cell wall (Caffall and Mohnen, 2009). It determines cellular shapes, tissue biomechanics, and the overall morphology of the organism (Höfte and Voxeur, 2017). Ultimately the growth process in plants depends on the cell wall expansion allowing cell enlargement..

While evolvability of genes and traits may promote specialization during species diversification, how ecology subsequently restricts such variation remains unclear. Chemosensation requires animals to decipher a complex chemical background to locate fitness-related resources, and thus the underlying genomic architecture and morphology must cope with constant exposure to a changing odorant landscape; detecting adaptation amidst extensive chemosensory diversity is an open challenge. Phyllostomid bats, an ecologically diverse clade that evolved plant-visiting from an insectivorous ancestor, suggest the evolution of novel food detection mechanisms is a key innovation: phyllostomids behaviorally rely strongly on olfaction, while echolocation is supplemental. If this is true, exceptional variation in underlying olfactory genes and phenotypes may have preceded dietary diversification. We compared olfactory receptor (OR) genes sequenced from olfactory epithelium transcriptomes and olfactory epithelium surface area of bats with differing diets. Surprisingly, although OR evolution rates were quite variable and generally high, they are largely independent of diet. Olfactory epithelial surface area, however, is relatively larger in plant-visiting bats and there is an inverse relationship between OR evolution rates and surface area. Relatively larger surface areas suggest greater reliance on olfactory detection and stronger constraint on maintaining an already diverse OR repertoire. Instead of the typical case in which specialization and elaboration is coupled with rapid diversification of associated genes, here the relevant genes are already evolving so quickly that increased reliance on smell has led to stabilizing selection, presumably to maintain the ability to consistently discriminate among specific odorants — a potential ecological constraint on sensory evolution.Significance StatementThe evolutionary relationship between genes and morphology is complex to decipher, and macroevolutionary trends are often measured independently; this is especially challenging to quantify in unstable genomic regions or hypervariable traits. Odorant cues are detected by proteins encoded by the largest and fasted-evolving gene family in the mammalian genome and expressed in epithelia distributed on elaborate bony structures in the nose, posing a challenge to quantification. Yet, the direct interaction of the olfactory system with environmental signals strongly suggest that selection shapes its immense diversity. In neotropical bats, where reliance on plant-visiting evolved from an insectivorous ancestor, we discovered clear dietary differences amongst species, but only after considering morphological and molecular data simultaneously, emphasizing the power of a coupled analysis.

Wavy walls built by nanofilaments In the model plant Arabidopsis , pavement cells fit together with the lobes and curves of jigsaw puzzle pieces. Such complex cell shapes, in plants, were generally thought to be driven by turgor pressure. Haas et al. now show that the extracellular cell wall can actively shape the cell it contains without relying on turgor pressure. Nanofilaments of pectin homogalacturonan in the cell wall shift between crystalline and anisotropic phases according to whether they are methylated. The shift in form drives changes in cell wall shape that stand independent of turgor pressure. Science , this issue p. 1003

In mammals, social and reproductive behaviors are mediated by chemical cues encoded by hyperdiverse families of receptors expressed in the vomeronasal organ. Between species, the number of intact receptors can vary by orders of magnitude. However, the evolutionary processes behind variation in receptor number, and its link to fitness-related behaviors are not well understood. From vomeronasal transcriptomes, we discovered the first evidence of intact vomeronasal type-1 receptor (V1r) genes in bats, and we tested whether putatively functional bat receptors were orthologous to those of related taxa, or whether bats have evolved novel receptors. Instead of lineage-specific duplications, we found that bat V1rs show high levels of orthology to those of their relatives, and receptors are under comparative levels of purifying selection as non-bats. Despite widespread vomeronasal organ loss in bats, V1r copies have been retained for >65 million years. The highly conserved nature of bat V1rs challenges our current understanding of mammalian V1r function and suggests roles other than conspecific recognition or mating initiation in social behavior.

Diversification and adaptive radiations are tied to evolvability, which in turn is linked to morphological integration. Tightly integrated structures typically evolve in unison, whereas loosely integrated structures evolve separately. Highly integrated structures are therefore thought to constrain evolutionary change by limiting morphological disparity. Mounting evidence suggests that high integration may facilitate evolutionary change along a single trajectory. We used geometric morphometrics to compare cranial disparity and integration among phyllostomid bats—which exhibit the greatest dietary diversity of any mammalian family— and their sister taxa within the superfamily Noctilionoidea. Our results reveal that phyllostomids are more tightly integrated and have less disparity in cranial shape than their outgroups, despite exhibiting tenfold higher species richness and significantly increased rates of speciation. Phyllostomid cranial morphology appears to have diverged from that of other noctilionoids by evolving along a single axis of morphological variation that describes the relative length of the rostrum. We propose that phyllostomids were able to evolve to occupy a wide range of dietary niches by varying rostrum length, possibly along a line of least evolutionary resistance. This study provides a compelling empirical example of how increased integration can lead to adaptation, implying that both high and low integration can underlie diverse phenotypes in adaptive radiation.