Abstract
In this Q&A, Cell Press Community Review Product Manager Matt Pavlovich talks to Martin Riccomagno about his paper “A genetic tool for the longitudinal study of a subset of post-inflammatory reactive astrocytes” and his experience with Cell Press Community Review.
Main text
Cell Press Community Review is a program where authors can submit their research papers for simultaneous consideration at multiple journals. Authors who submit to Community Review receive comments on the suitability of publication in a range of Cell Press research journals requested by the authors and suggested by the Community Review editorial team. A central aim of Community Review is to streamline the publication process by helping authors discover which Cell Press journal would be the best fit for their research. Here, Martin Riccomagno explains his research on post-inflammatory reactive astrocytes and discusses the experience of publishing his research in Cell Reports Methods after submitting to Community Review.
Can you briefly explain what your Cell Reports Methods paper is about?
Astrocytes are the most abundant cell type in the central nervous system (CNS) and ordinarily execute vital processes for proper brain function. However, they reprogram into “reactive” astrocytes (RAs) following injury. Astrocytes become reactive to varying degrees in virtually all neurodegenerative diseases and brain injury models. The role of RAs in progression or mitigation of brain disorders and disease has remained debated and largely unknown. Traditional astrocyte promoters such as GFAP or Aldhl1 are expressed by both healthy and reactive astrocytes, limiting their effectiveness for selectively manipulating gene expression only in RAs. In our paper, we describe the generation of an inducible approach to selectively target, label, and manipulate a subset of reactive astrocytes in brain disorders and disease. The biggest advantage of the newly developed transgenic model is that it can be used to perform longitudinal analysis of reactive astrocyte morphology, function, and gene expression. We then used this tool to answer an important biological question. In the case of reactive gliosis during acute inflammation the initial markers of reactivity that astrocytes display soon after the insult are no longer observed 1 month after inflammation has subsided. A long-standing question in the field was whether downregulation of RA markers during resolution of inflammation was because these astrocytes revert back to a non-reactive state or die and are replaced. This question had proven difficult to answer using the preexisting tools. Using the new approach, longitudinal analysis of brains during and after the resolution of acute inflammation revealed that RAs that are labeled soon after acute inflammation survive for at least 1 month. Furthermore, expression of specific markers associated with astrogliosis revert back to baseline after 1 month in the labeled cells, while one morphological feature of reactivity remains unchanged after 1 month. Our data indicate that the previously observed downregulation of RA markers 1 month after inflammation is likely due to changes in gene expression and not because of programmed cell death. Overall, our findings suggest that cellular changes associated with astrogliosis after acute inflammation can be temporary and largely reversible.
How did you become interested in this research? What motivated you to work in this field?
This really arose very organically from interacting with my office neighbor and close colleague, Todd Fiacco. We were discussing some experiments that he wanted to do to understand astrocyte biology in different disease models, and soon it became very clear that there was a need for better tools to address the questions that he wanted to answer. He brought to my attention a recent paper at the time by Jennifer Zamanian in the Ben Barres lab at Stanford on transcriptome profiling of reactive astrocytes in different injury models. Zamanian and coworkers identified specific markers that were highly upregulated by reactive astrocytes. We quickly realized that we could use promoters of these upregulated transcripts to generate a reactive astrocyte-specific Cre transgenic mouse line. Todd first checked with the late Dr. Barres to see if his group was already in progress making such a tool. I started reading more on the topic of reactive gliosis and found it fascinating. We also thought that our complementary expertise in astrocyte biology and neurogenetics would be ideal to tackle this sort of problem. We got a little bit of seed money from UC Riverside to make the mouse and started working on this almost immediately. With some initial characterization of the new mouse line, Todd and I were able to secure funding from the NIH to continue the work. Dr. Emma Wilson, an expert in neuroinflammation, joined us soon after, bringing with her all her knowledge and experience in the field. In many ways, the assembly of this team is the result of our Center for Glial Neuronal Interactions at UCR, which fosters the exchange of ideas and collaborations. I think this whole project is a testament to having people in close physical proximity to facilitate informal scientific interactions but also to having forums where scientists from different departments across campus can discuss new ideas and find common interests. In the end, I couldn’t have asked for better collaborators.
How did you decide to submit to Community Review? Were you familiar with Community Review beforehand?
We were looking for options where a manuscript would be considered by multiple journals at the same time. We had tried a slightly different model before where reviews are agnostic to journals within a consortium with good results. We were very happy to hear thar Cell Press had developed a new platform to do something similar. The main difference is that for Community Review, you pick the journals up front, and reviewers know what journals the authors are aiming for. Also, in the Community Review system, the editors of the individual journals agree upfront to send the paper out for review instead of having to shop around for a journal after the fact. In the end, we really liked the Community Review system.
What was the initial submission process like? Did you receive any editorial feedback on your manuscript?
The initial submission was very simple and streamlined. The only difference between the Community Review submission and a regular submission to a journal was that you could select several journals at the same time. This in a weird way felt empowering!
The editorial feedback came in the form of recommending consideration of additional journals that we didn’t think about originally. This was very useful, since we hadn’t selected Cell Reports Methods during the initial submission, yet it was a great fit in the end.
What was the review process like? How did the reviewer comments improve your paper or change its direction?
We thought the review process was excellent. The editors for Community Review were very helpful and kept an open line of communication. After the initial editorial process, the reviews came back promptly, and the reviews for the revision were even faster. More importantly, the process was very transparent.
The reviewers brought up some concerns and made several suggestions during our initial submission. We thought the comments were fair and on point, even the ones that were more critical. We tried to address most of these with new experiments and analysis. While the overall conclusions of the study didn’t change much, we think the revised manuscript is leaps better than the original submission in great part because of the reviewers’ constructive comments.
How about the revision process? Did you revise with a single journal in mind, or were you open to considering multiple journals when you resubmitted?
We considered more than one journal when we resubmitted. For one of the journals, we only needed to do minor revisions. However, for Cell Reports Methods it was actually a soft reject/major revisions situation. After consulting with the editors, we decided to embark on several new experiments to address the great majority of the reviewers’ comments. The reasoning behind that was that it would give us a chance at publishing in a “higher impact” journal but, more importantly, would improve the manuscript overall in the event that Cell Reports Methods didn’t accept it.
How did you ultimately decide on Cell Reports Methods?
We were given two options and thought that both were very good. However, and despite Cell Reports Methods being a new journal, we thought that Cell Reports Methods was a better fit for our study. Cell Reports Methods has a more focused scope than the other journal that also accepted our paper, and thus we thought it would be a better way to reach the right audience. We really wanted to highlight the new tools that we developed and felt like a methods-type journal would better accomplish this. We also viewed it as similar in profile as Cell Reports and have seen how other recent Cell Reports family journals have been very successful in publishing impactful work.
What are your thoughts on the evolution of peer review more broadly? Do you have any experience with non-traditional systems like zero-blind, double-blind, collaborative, or post-publication review? How can journals innovate in this area to better support authors?
I think those are all great ideas, and it would be important to have some mix of those moving forward. I personally think that double-blind is a better solution than zero-blind. Both should help in mitigating implicit bias and the occasional personal attack and/or unprofessional review. However, my impression is that reviewers in the early stages of their careers might not be willing to recommend rejection of a paper or ask for major revisions for fear of retaliation. That is why I think double-blind is a little better.
Our experience with collaborative reviews has been more of a mixed bag. I think it can work really well, but the rules need to be clear upfront. Sometimes it is not clear to what extent the manuscript should be revised during the first response to reviewers’ comments. Sometimes reviewers don’t understand the system and are unwilling to engage in discussion, defeating the purpose of the approach. I believe these can be easily solved by addressing them up front. We haven’t tried post-publication review, but we normally preprint our papers before or during submission.
Finally, I think the idea of having review consortia is definitely a step in the right direction to facilitate publishing. It can save a lot of time for everyone. So far we’ve had really good experiences with somewhat different strategies like Cell Press Community Review and Review Commons.
Members of the Riccomagno lab at the University of California, Riverside