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PONE-D-23-11890Key transcriptional effectors of the pancreatic acinar phenotype and oncogenic transformationPLOS ONE

Dear Dr. MacDonald,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised below during the review process by the reviewers.

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Surinder K. Batra

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors of the current manuscript present a descriptive study to describe the role four DNA-binding transcription factors in transcription regulation using a detailed transcriptional approach. While the study does a great job in describing these roles, there are some questions that would still need clarification:

1. While the identification of the four TFs is explained really well in the results, an explanation of the study design at the start of the results section will help the flow of the manuscript tremendously. This can be added as text or as a flow chart in the supplementary figures.

2. Figures 1c and 1g are missing axis labels and need an explanation of what the change values signify- is this a fold change value? Is it an absolute expression value?

3. The transition in between the various sections of the results section is rather abrupt and requires significant changes to help readers follow the study properly. Authors should consider adding explanations to next steps and why they decided to pursue a specific direction. As an example, the switch from study metabolic differences to transcriptomics has no explanation of transition.

While the extensive work the authors have put in is well appreciated, in the current

the manuscript is extremely hard to follow. The authors should consider revising the text extensively in order for it to have the anticipated impact in the field.

Reviewer #2: This manuscript does an excellent job demonstrating the roles of four DNA-binding transcription factors dTFs (Ptf1a, Nr5a2, Foxa2, and Gata4) on the differentiation state of pancreatic acinar cells (PACs). In addition, the study showed the regulatory effects of the dTFs cKO with its effects on KRAS oncogenic transformation (G12D)

Minor edit: There were several abbreviations mentioned in the main text or figure legend without full names (EST, MDS, and CPDB); I would advise the authors to include the full name.

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Reviewer #1: No

Reviewer #2: No

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Key transcriptional effectors of the pancreatic acinar phenotype and oncogenic transformation

PONE-D-23-11890R1

Dear Dr. MacDonald,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Surinder K. Batra

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: (No Response)

Reviewer #2: This manuscript does an excellent job demonstrating the roles of four DNA-binding transcription factors dTFs (Ptf1a, Nr5a2, Foxa2, and Gata4) on the differentiation state of pancreatic acinar cells (PACs). In addition, the study showed the regulatory effects of the dTFs cKO with its effects on KRAS oncogenic transformation (G12D). The authors did a great work addressing the comments.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

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