Evaluated articles

eLife assessment

This important study reports that Foxc2+ cells in the testis represent the quiescent spermatogonial stem cells (SSCs). The data supporting this claim are solid. The finding is of great significance to reproductive and stem-cell biology as male fertility depends on the fine balance between self-renewal and differentiation activities of the male germline stem cells, i.e., SSCs.

eLife assessment

This work presents important findings regarding the use of soil environmental DNA for non-invasive monitoring of the endangered kākāpō parrot population in New Zealand. The approach based on sequence analysis is convincing but comparisons to established methods are lacking. The tools presented in this study are innovative and will be relevant to those working with environmental DNA and the conservation of biodiversity.

eLife assessment

This valuable data study presents convincing data that expression of the C. elegans transcription factor NHR-67 is sufficient to drive an invasive fate, and that the alternative proliferative fate is associated with NHR-67 transcriptional down-regulation. While the observation that NHR-67 forms punctae associated with transcriptional repressors in non-invasive cells is intriguing, the work does not yet established a clear link between the formation and dissolution of NHR-67 condensates with the activation of downstream genes that NHR-67 is actively repressing. The work will be of interest to developmental biologists studying transcriptional control of cell fate specification in animals, especially once issues around the functional significance of the NHR-67 contiaining punctae are resolved.

eLife assessment:

This manuscript describes development of a new algorithm for integrative analysis of multi-omics data. This work should be of potential interest to scientists performing bioinformatic pathway discovery in multi-omic datasets especially those that relate to signaling.

eLife assessment

This manuscript presents valuable findings that bring together two important topics in cell biology: the function of membrane contact sites and cell migration. The authors describe a role of the ER tether protein VAP-A in focal adhesion dynamics and cell motility. Although the authors present solid evidence to support some of the main claims of the paper, some of the other claims would benefit from stronger experimental support. Nonetheless, this paper will be of interest to those cell biologists and biophysicists working on adhesion, migration, and membrane contact site biology.

eLife assessment

This paper is of interest for skeletal biologists studying bone marrow stem/progenitor cells and bone remodeling. Using Adipoq-Cre-driven conditional deletion of Csf1 that encodes M-CSF and reanalyzing publicly available scRNAseq data, the authors recognize a subpopulation of bone marrow cells (i.e. AdipoQ-lineage progenitors) as an important source of M-CSF. The authors found that M-CSF production from these bone marrow cells influences the development of macrophages and osteoclasts as well as bone mass, including the bone loss associated with estrogen deficiency. This is a clearly written and nicely presented study that has potential to offer important new information regarding the source of M-CSF in the bone marrow.

eLife assessment

This study provides a valuable data resource to study the systemic effects of severe COVID-19. It shows compelling evidence that the transcriptional response to COVID-19 is coordinated across the body, and it highlights cell interactions between macrophages and endothelial cells in COVID-19. This analysis and the associated resource will be valuable to understand the pathogenic mechanism of long-COVID.

eLife assessment

This important study develops a new technical advancement in ex vivo live imaging of hematopoietic tissues to monitor blood cells in their native microenvironment. The new method for live imaging and tracking is compelling, and the strength and breadth of hematopoietic analysis are convincing. This work provides a very useful new system for immunologists and cell biologists, which will supply new perspectives on the system-level mechanisms of cell differentiation and innate immunity.

eLife assessment

This paper is of interest to immunologists conducting single-cell analyses of T-cell recognition. It provides a means of curating datasets to ensure T cell-antigen pairs are identified. The data generated through this method often suffers from a relatively high background, so the authors present a computational approach to enhance the signal-to-noise of this type of analysis. At this stage, it is unclear if the thresholds and filtering steps described by the authors can be generally applied to other datasets of different qualities than the one used here.

eLife assessment

This study presents a valuable mathematical model for the adaptive dynamics of cancer evolution in response to immune recognition. The mathematical analysis is rigorous and convincing, and overall the framework presented could be used in the future as a solid base for analytically tracking tumor evasion strategies. However additional discussion is needed to clarify certain gaps between the theory and cancer evolution in real systems. The work will be of interest to evolutionary cancer biologists and potentially it may also have implications for the design of clinical interventions.

eLife assessment

This study presents a valuable finding on the critical features and patterns of m1A modification and in neurons and OGD/R-treated neurons. Moreover, the authors identified m1A modifications on different RNAs and explored the possible effects of m1A modification on the functions of different RNAs via an integrated approach of omics and bioinformatics. The evidence supporting the claims of the authors is solid, although inclusion of more in-depth studies to analyze the transcription factors for the upstream regulation would have strengthened the study. The work will be of interest to neurobiologist and scientists in the field of RNAs.

eLife assessment

Scott et al use Drosophila as a model to study the sialylation pathway and its role in nervous system function. Surprisingly, they find that the critical substrate for sialylation, CMP-Neu5Ac, is 'outsourced' to glia. This significant study presents a new twist in mechanisms underlying protein glycosylation and uncovers a new layer in the complex interplay of neurons and glia.

eLife assessment

This study links chromatin remodeling with antifungal drug resistance in Cryptococcus neoformans. The work is important because it reveals a new facet of how drug resistance can emerge and associates. The work presented is well done but the story is incomplete since there are questions about methods and association that need to be addressed. Establishing a link between chromatin remodeling and antifungal resistance is a finding that would be of interest to infectious disease researchers, cell biologists, and drug developers.

eLife assessment

This study uses a combination of compelling biochemical and genetic approaches to identify a highly mutagenic DNA polymerase, which drives a wide spectrum of mutations when overexpressed. The important findings advance the understanding of mutagenesis in mycobacteria. The work will be of interest to bacteriologists interested in mutagenesis and the emergence of drug resistance.

eLife assessment

There are many strengths in this paper that examines patterns of epididymal blood and lymphatic vasculature, supported by quantitative methods, and well-conducted 3D imaging studies (graphics and videos). Minor weaknesses include the lack of higher magnification images and the organization of image panels in some figures. Overall, this is a very important contribution to the epididymis research field.

eLife assessment

This study, of interest to population geneticists and evolutionary biologists alike, aims at investigating temporal variation in patterns of germline mutation during the evolution of human populations. The authors suggest that shifts in mutation spectra occur frequently, over a few thousands of generations, possibly as a consequence of changes in environmental exposure, or of genetic modifiers. There are several important aspects of methodology that need to be clarified, and several additional tests have to be done to confirm that the reported observations are not the result of methodological artifacts. The paper also overstates certain weaknesses of previously published papers on mutation spectrum evolution as well as the generation time hypothesis; correcting these oversimplifications would more accurately capture what the paper's new analyses add to the state of knowledge in these areas.

eLife assessment

This manuscript provides compelling evidence that macrophages transfer mitochondria to cancer cells and that transferred mitochondria stimulate proliferation in recipient cells. The usage an array of clever cell biology-based tools provides compelling evidence for these claims despite the difficulties associated with studying a relatively low probability event. Solid evidence supports the proposed model that transferred mitochondria induce proliferation by stimulating ERK signaling in a ROS dependent manner, although at present some aspects of the proposed model are incomplete. The work has broad significance for both mitochondrial biology and cancer biology as the authors show clear evidence of mitochondrial transfer in mouse models of human tumors.

eLife assessment

Opioid-induced respiratory depression is one of the side effects of opioid drugs. Although opioid overdose deaths are highly prevalent, our knowledge of the neural circuits underlying respiratory depression in the brainstem is far from complete. The present study used a variety of sophisticated experimental techniques to convincingly reveal the identity of brainstem components that are part of the neural circuits involved in the mediation of opioid respiratory effects, together with defining potential synaptic underlying mechanisms. They focused on two regions of the brainstem, namely the Kolliker-Fuse and the preBötzinger Complex, and proposed a combination of three complementary processes at pre- and post-synaptic sites in both KF and preBötC regions to explain respiratory depression linked to opioid exposure. This study provides very important findings on the circuitry involved in opioid-induced respiratory depression, and the present results are of broad interest to the respiratory control research community, as well as medically relevant.

eLife assessment

Candida morphogenesis is important for virulence. This study provides important new information as to how C. albicans regulates the switch from budding to hyphal morphology. Their results identify transcription factors involved in the process of hyphal morphogenesis in the host. The results are convincing and will be interesting to scientists in the fields of medical mycology and cell biology.

eLife assessment

This manuscript analyzes large-scale Neuropixels recordings from visual areas and hippocampus of mice passively viewing repeated clips of a movie and reports that neurons respond with elevated firing activities to specific, continuous sequences of movie frames. The important results support a role of rodent hippocampal neurons in general episode encoding and advance understanding of visual information processing across different brain regions. The strength of evidence for the primary conclusion was found to be convincing.