At Cell Press, we're all very committed to the value of peer review and the role it plays in the effective and accurate communication of science.

So we're always excited when Peer Review Week comes around, as it's a great opportunity to highlight that value and recognize all the important work that peer reviewers do. This year is no exception, and on top of general recognition, we've also been thinking more specifically about this year's Peer Review Week theme of transparency in peer review.

As reviewers and editors, we have a front row seat for seeing how much papers change and improve as a result of peer review. Some papers, of course, move through from submission to publication with very few changes, but we find that in many (most) cases reviewers and editors make constructive suggestions that help to shore up what's shown, fill in logical gaps, address inconsistencies, or improve the interest and relevance of the work by enhancing the level of insight.

While authors are often very appreciative of constructive input, readers are blissfully unaware of how much peer review helped shape the final manuscript, as all of that work happens behind the scenes. So, we have been thinking about how we can overcome that information gap in a way that improves transparency and helps highlight the value that peer review adds to a final paper.

Some journals have already made a start by publishing reviewer comments and even decision letters. We've also considered that approach, but we found it difficult to envision how we could capture the entire review process in a clear way that would be useful to readers. At least for Cell Press, the review process is complex, involving several different discussions between the editor and the reviewers as well as the editor and the authors. Finding a way to share all of that information effectively while still maintaining the confidentiality that all of the participants expect is challenging.

So we thought from the reader's perspective about what we could do instead to capture and surface the key information from the review process, and we've come up with an idea inspired by an approach we've already seen some authors take when they send response letters for us and the reviewers: a table of what has changed in the paper and which comment or suggestion the change is designed to address. As editors, we appreciate the level of clarity this simple format provides and thought that something like this could be useful to include with a published paper without distracting from the final message of the work.

To test this idea, we turned to a recent Cell Stem Cell author, Hai-Hui (Howard) Xue from the University of Iowa. We knew that Howard appreciated how much his paper improved as a result of reviewer input and editorial guidance because he gratefully told us so as it moved forward to publication! This also seemed like a good test example for our experiment because we knew that the revisions were substantial, more so than for a number of our papers, and would therefore be a relatively complex set of changes to try to represent. The Xue team's paper published online on August 24 and appears in the September issue of Cell Stem Cell.

We contacted Howard Xue and asked if he'd like to participate in our experiment, and were excited that he agreed without hesitation. Howard then sent us a summary of the changes and additions to the paper that resulted from the peer review process, and we worked with him to put those together into the table that you can see below.

The main point of the Xue team's paper is to introduce a new idea for a potential combination therapy approach to treat chronic myelogenous leukemia (CML) in conjunction with the chemotherapy medication imatinib. As indicated at the top of the table, during the review process Howard and his colleagues developed the paper in two main ways: (1) improving the insight into the molecular mechanisms involved, to help understand the basis of the effects that they see and clarify why their findings differ from previous related reports, and (2) strengthening the evidence that the work is likely to have translational relevance. We limited the table to the points that the authors addressed experimentally in order to improve the paper, and we haven't included questions or suggestions that came up in the review process but fell outside of the revision scope.

BROAD REVISION AREAS REQUEST CHANGES IMPACT Better understand the molecular mechanism by which PGE1 impairs CML LSCs. Developed understanding beyond the original interpretation that PGE1 has a broad impact on the transcriptional program in LSCs. Revisions clarified the mechanistic pathway and pinpointed a specific set of target genes, AP1 family transcription factors, which were potently repressed by PGE1 treatment. Enhance the evidence that the findings are likely to have translational relevance. Expanded study on xenograft model of transplanting human CML LSCs into immunocompromised mice. Demonstrated a synergistic effect of PGE1 with conventional CML therapy in LSC inhibition. Also suggested that AP-1 factors could provide new therapeutic targets and biomarkers for assessing therapeutic efficacy and prognosis in CML treatment. SPECIFIC FIGURE CHANGES ORIGINAL DATA REQUEST & CHANGES IMPACT Figure 1: Analysis of WT and Tcf1/Lef1-deficient HSCs for transcriptomic changes. Expand analysis in Figure 1 to LSCs (Rev1&2). Updated Figure 1A B S2 Expanded analysis of WT and Tcf1/Lef1-deficient HSPCs as well as WT and Tcf1/Lef1-deficient CML LSCs. Figure 1: Transcriptomic analysis suggested a link between Tcf1/Lef1 and HSC stemness, cell cycle regulation and AP1 family transcription factors. More extensively characterize the suggested link between Tcf1/Lef1 and AP1 family transcription factors (Rev1,2&3). Updated Figure 1C , S1 Strengthened the connection between Tcf1/Lef1 and AP1 factors, particularly in LSCs. Figure S1A New observation that AP1 expression is elevated in LSCs relative to WT HSPCs in the murine model. Addition of Figure 1D Further confirmation of the new observation on elevated AP1 expression in human CML LSCs compared to human HSPCs. Figure 2: Identification of PGE1 based on Tcf1/Lef1-dependent genes using CMAP, and demonstration of its impact on impairing LSCs in a murine model. Demonstrate similarity between PGE1 treatment and Tcf1/Lef1 genetic ablation (Rev3). Addition of Figure 2G H Showed that PGE1 treatment and genetic ablation of Tcf1/Lef1 have similar impact on CML LSCs and strengthened the idea that PGE1 treatment can elicit gene expression changes similar to those caused by Tcf1/Lef1 gene deletion. Figure 3: Used serial transplantation assays to characterize the impact of PGE1 treatment on LSCs. Include an LSC limiting dilution assay to strengthen the original conclusion (Rev3) Addition of Figure 3D Addition of LSC limiting dilution assays. These strengthened the evidence for the impact of PGE1 on functional LSCs by expanding beyond solely depending on cell surface markers to identify LSCs. Figure 4: Used a selected gene analysis (including AP1 factors) to show that PGE1 has a distinct effect from a highly related molecule PGE2 (differs in only one carbon-carbon double bond.) Expand transcriptomic analysis in LSCs on the effect of PGE1, with comparison with that of PGE2 and Tcf1/Lef1 gene deletion (Rev1&2). Updated Figure 4A B Included high throughput transcriptomic analysis of the distinct effect of PGE1 and PGE2 on LSCs, and further comparison with the changes caused by Tcf1/Lef1 gene deletion as described in Figure 1. Figure 4 second point Examine the functional link to AP1 factors and test whether AP1 is a major target of PGE1 treatment (Rev1,2&3). Addition of Figure 4C-G Focused analysis of the functional link to AP1 factors, showing forced expression of Fosb/Fos, but not Egr1 (another Tcf1/Lef1 target gene), in LSCs enhances propagation of CML and abrogates sensitivity to PGE1 treatment, thus identifying AP1 factors are major targets of PGE1. Figures 5 & 6: Used a selected gene approach (including AP1 factors) to show that Misoprostol, but not other EP receptor agonists, simulates the effect of PGE1, and deduced that EP4 receptor is the major receptor that PGE1 acts on in LSCs. Also used in vitro selected gene approach to show that EP4 deficiency abrogated the effect of PGE1 in LSCs. Further validate the in vitro data with in vivo evidence that EP4 receptor is the major receptor that PGE1 acts on in LSCs, and EP4 deficiency abrogates the effect of PGE1 in LSCs (Rev1&2). Addition of Figure 5C D Addition of in vivo data to show that EP4 deficiency largely abrogates the sensitivity of LSCs to PGE1 treatment. Figures 5 & 6 second point Clarify the results from the selected gene approach by examining the mechanistic specificity of PGE1 compared to PGE2 (Rev2). Addition of Figure 5E F Showed that unlike PGE2, PGE1 does not stabilize beta-catenin in LSCs (Figure 5E), and genetic ablation of beta-catenin does not affect PGE1 induced repression of AP1 genes (Figure 5F), thus clarifying that PGE1 treatment acts independently of beta-catenin. Figure 7: Used xenograft of human CML CD34+ LSCs or HSPCs to show the specific effect of PGE1 in impairing LSC engraftment. Examine whether there is synergy between PGE1 and TKI treatment on human CML LSCs (Rev3). Addition of Figure 7B C Applied an additional protocol to analyze the effect of PGE1 treatment on grafted LSCs, and investigated the synergistic effect of PGE1 and imatinib. Figure 7 second point Examine whether the mechanism used by PGE1 is conserved in murine model and human disease (Rev3). Addition of Figure 7D Gene expression analysis of PGE1-treated human CML LSCs, to show that AP-1 is a conserved target in human CML LSCs for PGE1 treatment, and might thus be used as a biomarker for disease and as a potential therapeutic target.

Our overall goal here is to use this type of table format as a clear way to communicate revisions that authors made during the course of the peer review process. Hopefully you as a reader can easily see from this table what the authors changed or added and how the paper improved as a result.

We're thinking that we could potentially introduce this type of table, or an improved version of it, as part of our overall transparency efforts and as a complement to STAR Methods. If it proves popular and successful, it could even become something that we offer to all authors as an option for their publication process.

At this point, this table of revisions concept is still in its early days, and we'd really love your feedback! So...

Do you like this idea?

Do you think this approach is useful?

Do you have any suggestions for ways it could be improved?

Would you find something like this useful when reading a paper?

Do you have ideas about how it could be simplified or condensed and yet still convey the key information that you would want to see?

Perhaps most importantly, would you as an author be interested in having something like this appear with your published paper?





Please let us know! It would be really helpful for us to get feedback to help us decide if or how to develop this idea further. Please comment on this post or send us an email at crosstalk@cell.com.