Genetics

Integrating bulk and single cell RNA-seq refines transcriptomic profiles of individual C. elegans neurons

1. Alec Barrett
2. Erdem Varol
3. Alexis Weinreb
4. Seth R Taylor
5. Rebecca M McWhirter
6. Cyril Cros
7. Berta Vidal
8. Manasa Basaravaju
9. Abigail Poff
10. John A Tipps
11. Maryam Majeed
12. Chen Wang
13. Emily A Bayer
14. Molly Reilly
15. Eviatar Yemini
16. HaoSheng Sun
17. Oliver Hobert
18. David M Miller
19. Marc Hammarlund

• Curated by eLife

  eLife Assessment

  This valuable paper provides refined gene expression datasets for 52 neuron classes in C. elegans using a new method that takes advantage of the complementary strengths of bulk sequencing of flow-sorted cells and single-cell sequencing. In general, support for the paper's findings is convincing. However, more rigorous consideration of some of the method's statistical assumptions and validation of the predicted gene sets would improve the work.

Reviewed by eLife

PWWP-ADD and N-terminal domains of DNMT3B1 confer specificity for developmentally regulated CpG island methylation

1. Komal Yasmin
2. Tatyana B Nesterova
3. Neil Brockdorff

Reviewed by Review Commons

TRPγ regulates lipid metabolism through Dh44 neuroendocrine cells

1. Dharmendra Kumar Nath
2. Subash Dhakal
3. Youngseok Lee

• Curated by eLife

  eLife Assessment

  This important study reports findings that Trpγ, a type of transient receptor potential (TRP) channel expressed in Dh44-releasing neuroendocrine cells, mediates starvation-dependent lipid catabolism. Overall, the claims of the authors are supported by solid evidence. The work should be of interest to both basic and medical biologists working on lipid metabolism.

Reviewed by eLife

Functional characterization of all CDKN2A missense variants and comparison to in silico models of pathogenicity

1. Hirokazu Kimura
2. Kamel Lahouel
3. Cristian Tomasetti
4. Nicholas J Roberts

• Curated by eLife

  eLife Assessment

  This is a saturation mutagenesis screening of CDKN2A gene, successfully assessing the functionality of the missense variants. The work is solid and well-prosecuted. The manuscript was improved during the revision process and this work will serve as a valuable resource for diagnostic labs as well as cancer geneticists.

Reviewed by eLife

Molecular Requirements for C. elegans Transgenerational Epigenetic Inheritance of Pathogen Avoidance

1. Rachel Kaletsky
2. Rebecca Moore
3. Titas Sengupta
4. Renee Seto
5. Borja Ceballos-Llera
6. Coleen T. Murphy

• Curated by eLife

  eLife Assessment

  This fundamental study concerns a model for transgenerational epigenetic inheritance, the learned avoidance by C. elegans of the PA14 pathogenic strain of Pseudomonas aeruginosa. The authors test the impact of procedural alterations made in another study, by Gainey et al., which claimed that transgenerational inheritance in this paradigm lacks robustness, despite this observation having been reported in multiple papers from the Murphy lab. The authors of the present study show that by following a non-standard avoidance protocol, Gainey et al. likely biased their measurements in a way that made it hard to observe learned avoidance. The authors also highlight the importance of bacterial growth conditions, showing that expression of the trigger molecule, the bacterial P11 RNA, which is necessary and sufficient to drive the transgenerational inheritance of the avoidance phenotype, is influenced by temperature. As expression of P11 was not verified by Gainey et al., this provides another explanation for the inability to observe transgenerational epigenetic inheritance. Together, the authors provide compelling and powerful arguments that the original phenomenon is robust and that it can be reproduced in the Murphy lab by following their original protocol precisely, including the use of azide to immobilize the worms at the food source. Overall, this study not only provides guidance for investigators in this experimental paradigm, but it also provides additional understanding of the differences between naïve preference, learned preference, and transgenerational epigenetic inheritance. The present study is therefore of broad interest to anyone studying genetics, epigenetics, or learned behavior.

Reviewed by eLife

Diverse Genotype-by-Weather Interactions in Switchgrass

1. Alice H MacQueen
2. Li Zhang
3. Samuel Pattillo Smith
4. Jason E Bonnette
5. Arvid R Boe
6. Philip A Fay
7. Felix B Fritschi
8. David B Lowry
9. Robert B Mitchell
10. Francis M Rouquette
11. Yanqi Wu
12. Arbel Harpak
13. Thomas E Juenger

• Curated by eLife

  eLife Assessment

  The study reports valuable findings on the nature of genotype-by-climate interaction, parameterised in a framework that allows integrating genetics and ecophysiological variation in switchgrass. The evidence provided is solid overall but the analysis could be improved to better support some of the claims.

Reviewed by eLife

A mathematical model that predicts human biological age from physiological traits identifies environmental and genetic factors that influence aging

1. Sergiy Libert
2. Alex Chekholko
3. Cynthia Kenyon

• Curated by eLife

  eLife Assessment

  This important study developed a mathematical model to predict biological age by leveraging physiological traits across multiple organ systems. The results presented are convincing, utilizing comprehensive data-driven approaches. However, additional external validation could further strengthen its generalizability. The model provides a way to identify environmental and genetic factors impacting aging and lifespan, revealing new factors potentially affecting aging. It also shows promise for evaluating therapeutics aimed at prolonging a healthy lifespan.

Reviewed by eLife

The robust, high-throughput, and temporally regulated roxCre and loxCre reporting systems for genetic modifications in vivo

1. Mengyang Shi
2. Jie Li
3. Xiuxiu Liu
4. Kuo Liu
5. Lingjuan He
6. Wenjuan Pu
7. Wendong Weng
8. Shaohua Zhang
9. Huan Zhao
10. Kathy O Lui
11. Bin Zhou

• Curated by eLife

  eLife Assessment

  The study by Chi and colleagues presents important new tools for precise genetic manipulation and lineage tracing in mice. The characterization of these new models was conducted using validated, state-of-the-art methodologies and convincingly demonstrates their ability to enhance the precision of genetic manipulation in distinct cell types. This work will be of great interest to many laboratories worldwide and will facilitate future research across various biomedical disciplines.

Reviewed by eLife

ZC3H11A mutations cause high myopia by triggering PI3K-AKT and NF-κB mediated signaling pathway in humans and mice

1. Chong Chen
2. Qian Liu
3. Cheng Tang
4. Yu Rong
5. Xinyi Zhao
6. Dandan Li
7. Fan Lu
8. Jia Qu
9. Xinting Liu

• Curated by eLife

  eLife Assessment

  This work investigates ZC3H11A as a cause of high myopia through the analysis of human data and experiments with genetic knockout of Zc3h11a in mouse, providing a useful model of myopia. The evidence supporting the conclusion is still incomplete in the revised manuscript as the concerns raised in the previous review were not fully addressed. The article will benefit from further strengthening the genetic analysis, full presentation of human phenotypic data, and explaining the reasons why there was no increased axial length in mice with myopia. The work will be of interest to ophthalmologists and researchers working on myopia.

Reviewed by eLife

DNA replication in primary hepatocytes without the six-subunit ORC

1. Róża K Przanowska
2. Yuechuan Chen
3. Takayuki-Okano Uchida
4. Etsuko Shibata
5. Xiaoxiao Hao
6. Isaac Segura Rueda
7. Kate Jensen
8. Piotr Przanowski
9. Anthony Trimboli
10. Yoshiyuki Shibata
11. Gustavo Leone
12. Anindya Dutta

• Curated by eLife

  eLife Assessment

  This valuable descriptive manuscript builds on prior research showing that the elimination of Origin Recognition Complex (ORC) subunits does not halt DNA replication. The authors obtain solid data using various methods to genetically remove one or two ORC subunits from specific tissues and still observe replication. The replication appears to be primarily endoreduplication, indicating that ORC-independent replication may promote genome reduplication without mitosis. The mechanism behind this ORC-independent replication remains to be elucidated. The study and mutants described herein lay the groundwork for future research to explore how cells compensate for the absence of ORC and to develop functional approaches to investigate this process. The reviewers suggested the observations could be supported by additional experiments. This work will be of interest to those studying genome duplication and replication.

Reviewed by eLife, Review Commons