Cell Biology

eLife assessment

This study reports a potentially important discovery that testosterone-induced metabolic changes in seminal vesicle epithelial cells lead to the production of oleic acids in seminal plasma to enhance sperm fertility. The evidence to support metabolic changes in seminal vesicles and the identification of oleic acid as a key factor in seminal plasma is solid. However, the evidence for how oleic acids support enhanced sperm fertility in vivo is not well supported, thus currently remains incomplete, and requires further study.

eLife assessment

This study presents an important application of high-content image-based morphological profiling to quantitatively and systematically characterize induced pluripotent stem cell-derived mixed neural cultures cell type compositions. Convincing evidence through rigorous experimental and computational validations supports new potential applications of this cheap and simple assay.

eLife assessment

The development of this mouse model is an important step to establish the role of the FSH Receptor in tissues beyond the reproductive system, and the data provided in this paper are convincing for a role for the FSH receptor in cell systems well beyond the classic reproductive tissues. Such model(s) have long been needed in this field and will provide expanded opportunities to better define FSH biology in vivo in these important target tissues. Ultimately, this model could shed light on FSH biology in women after menopause, when endogenous FSH levels rise dramatically, or in men with hypogonadism when FSH levels are high.

eLife assessment

This important study identifies a novel link between the early keratinocyte response to wounds and the subsequent regenerative capacity of local sensory neurons. The evidence supporting the claims of the authors is solid, although the inclusion of additional pharmacological and genetic manipulations might have strengthened the mechanistic aspects. The work will be of interest to cell and developmental biologists interested in tissue regeneration and cell interactions in a broader context.

eLife assessment

This work describes a valuable new technique involving proximity labelling to identify Drosophila proteins modified by GlcNAcylation in subsets of cells in vivo. A solid set of experiments shows that several ribosomal proteins are modified in the fly mushroom body. Consistent with a role for GlcNAcylation of ribosomal proteins in control of memory related translational control, the authors show that perturbation of GlcNAc modification in KCs prevents efficient consolidation of long-term memory.

eLife assessment

In this important study, Xiong and colleagues studied PKA regulation in synaptic plasticity. They provide convincing evidence that dissociation of PKA catalytic subunits is essential for the proper function of the kinase. Experiments using a PKA regulatory-catalytic subunit fusion establish that dissociative activation is required for both structural long-term potentiation and basal priming of AMPA receptors.

eLife assessment

How the triplicate interaction between chemokines with both GAGs and G protein-coupled receptors (GPCR) works and how gradients are created and potentially maintained in vivo are poorly understood. The authors provide solid evidence to show phase separation can drive chemotactic gradient formation. The paper is a useful advance in the field of chemokine biology.

eLife assessment

This important study addresses a fundamental question: how do post-translational modifications of tubulin regulate the function of the microtubule cytoskeleton in vivo? The authors generate a large panel of tubulin mutants designed to lack specific modifications and describe their effects using endogenous editing and touch receptor neurons in C. elegans as an in vivo model. While the work presents an impressive amount of data, it is in part incomplete, since the presence and absence of specific tubulin modifications and their effects on microtubules are not demonstrated in all cases.

eLife assessment

This study presents valuable findings on the role of the Drosophila ubiquitin-conjugating enzyme UBE2D/eff in maintaining proteostasis during aging. Protein levels of UBE2D decrease with age, and knockdown of UBED2 leads to an accumulation of ubiquitinated proteins, and a shortened lifespan that can be rescued by ectopic expression of the human homologous gene. The work supports a role of this ubiquitin conjugating enzyme in proteostasis, although the evidence is still incomplete. The study will be of broad interest to cell biologists working in aging and age-related diseases.

eLife assessment

In this important study by Theriot et al., the authors utilize an impressive set of innovative approaches to conduct a CRISPRi pooled screen in human cells using large-scale microscopy screen data. They leverage an improved barcoding approach to identify genes targeted in specific cells and examine the effects on cell morphology using high-dimensional phenotypic analysis. The method and data presented are compelling.

eLife assessment

This important study identifies novel small molecule antagonists of CXCR4 that disrupt nanocluster formation and chemotactic function without blocking CXCL12 binding and downstream signals. The conclusions are based on solid evidence, but the work could be improved by including kinetic and dose information on the most active inhibitors. We also note that modeling and mutagenesis implicate helix V and VI in an allosteric mechanism, but that the description of the modeling is not sufficiently detailed such that others could replicate it.

eLife assessment

In their short technical report, Verma et al. describe how endogenously-tagged dynein and dynactin molecules localize to growing microtubule plus-ends and move processively along microtubules in cells. The authors present solid evidence that cytoplasmic dynein is a processive motor that takes long excursions prior to dissociating from microtubules. However, there are concerns about the robustness of the imaging and analysis protocols, which should be more clearly defined. This is a useful study that will be of interest to cell biologists and biochemists in the motor protein field.

eLife assessment

The authors examined in detail the epigenetic changes and alterations in the subnuclear arrangement of a unique var gene associated with Plasmodium falciparum placental malaria. Although the observations are mainly confirmatory, the findings are valuable for theoretical considerations and practical applications. Applying the latest methods for the analysis of histone marks, transcriptomics, DNA methylation, and chromosome conformation, the authors provide observations that are convincing, thus making their claims appropriate.

eLife assessment

This study is partly useful as it corroborates what is already known about the elevated proliferation capacity of mid lobular hepatocytes in liver regeneration. Lineage tracing and scRNAseq studies are powerful for the investigation of such heterogeneous hepatocyte proliferation capacity. Nevertheless, based on experimental limitations, incomplete method description and inadequate data analyses the presented data are insufficient to support the proposed conclusions of a mesenchymal-hepatocyte hybrid population in the murine liver.

eLife assessment

In their valuable study, Chen et al. aim to define the neuronal role of HMMR, a microtubule-associated protein typically associated with cell division. Their findings suggest that HMMR is necessary for proper neuronal morphology and the generation of polymerizing microtubules within neurites, potentially by promoting the function of TPX2. While the study is recognized as a first step in deciphering the influence of HMMR on microtubule organization in neurons, the reviewers note the current work is incomplete, with significant gaps and it would benefit from further exploration of the mechanism of microtubule stability by HMMR, the link between HMMR-mediated microtubule generation and morphogenesis, and the physiological implications of disrupting HMMR during neuronal morphogenesis.

eLife assessment

This valuable manuscript reports alterations in autophagy present in dopaminergic neurons differentiated from iPSCs in patients with WDR45 mutations. The authors identified compounds that improved the defects present in mutant cells by generating isogenic iPSC without the mutation and performing an automated drug screening. The methodological approaches are solid, but the claims still need to be completed: showing the effects of the identified compounds on iron-related alterations is crucial. The effects of these drugs in vivo would be a great addition to the study.

eLife assessment

This useful study investigates the role of the centrosomal protein CEP44 in centriole duplication and mitotic spindle formation. While the analysis of CEP44 mitotic phosphorylation and spindle recruitment is solid, the characterization of CEP44's role at centrioles is incomplete and would benefit from additional controls and analyses. Since the work links CEP44 reduced expression to poor survival in breast cancer patients, it is of interest not only to cell biologists but also to cancer researchers.

eLife assessment

This is a valuable study on K187 acetylation of the nuclear protein, TIP60, required for its phase separation and function. The evidence supporting the primary conclusion is incomplete and warrants more scrutiny.

eLife assessment

This study investigates the role of the bile acid receptor TGR5 in adult hematopoiesis of the mouse model. The findings are potentially useful because the loss of TGR5 leads to dysregulation of bone marrow adipose tissue (BMAT) that has emerging regulatory functions. However, the study is still incomplete because the mechanism of TGR5 is not clear, the stromal cells expressing TGR5 have not been well defined, and there is not strong evidence for the role of TGR5 in recovery from transplant stress.

eLife assessment

This solid study investigates the transdifferentiation of chicken embryonic fibroblasts into muscle and fat cells in 3D to create whole-cut meat mimics. The study is important and provides a method to control muscle, fat, and collagen content within the 3D meat mimics and thus provides a new avenue for customized cultured meat production. Limitations of this study include the use of transgene for transdifferentiation and thus the creation of GMO food.