PONE-D-22-26088Human embryonic stem cells secrete macrophage migration inhibitory factor: A novel findingPLOS ONE

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Author Contributions

Zhenqiang Zhao and Jingquan Li conceived and designed the work, took part in all the works. Yanzhao Wei and Xiaohan Zheng were responsible for experiments,statistical analysis and writing of the manuscript.Ting Huang,Shengtong Sun,Xufang Wei and Qibing Liu were responsible for data collection and statistical analysis.”

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Author Contributions

Zhenqiang Zhao and Jingquan Li conceived and designed the work, took part in all the works. Yanzhao Wei and Xiaohan Zheng were responsible for experiments,statistical analysis and writing of the manuscript.Ting Huang,Shengtong Sun,Xufang Wei and Qibing Liu were responsible for data collection and statistical analysis.”

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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: Partly

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

Reviewer #1: Yes

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

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Reviewer #1: Yes

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

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Reviewer #1: No

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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: This is an interesting and original paper that shows that MIF is also produced grom human embrionic stem cells.

The Authors also demonstrate that MIF acts in HESC via binding to CXCR2 and CXCR7 and not through convebtional receptors such as CD74 and CD44.

While the finding is original and of interest its biological meaning remains elusive.

I have several points of concerns on the paper as it stands:

1. have the Authors evaluated whether HESC also secrete MIF-2 (DDT) ? There is no mention to MIF2 (DDT) in the paper and this point is of particular interest (PMID 30439447; PMID 30682543). In anycase the existence and possible secretion of DDT from HESC needs to be discussed

2. For search of completeness the Authors should discuss that MIF is implicated in several autoimmune diseases (PMID 18721909)

3. The statement that MIF suppresses tumour formation needs to be restated as the action of MIF in oncogenesis is complex and often dicothomic and may also favour tumor formation and progression (PMID 32769903; PMID 32155795; PMID 31867451; PMID 3334425)

4. As several specific MIF inhibitors are being developed and a semispecific inhibitor, ibidulast is already in the clinical setting, the present finding of the Authors of MIf production from HESC and the discussed potentil role of MIF in embryogenesis makes it important to mention that MIF inhibition during pregnancy should be carefullly evaluated

5. the paper is too long and could be reduced by 20%

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Reviewer #1: No

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Human embryonic stem cells secrete macrophage migration inhibitory factor: A novel finding

PONE-D-22-26088R1

Dear Dr. zhao,

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.

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Michael Klymkowsky, Ph.D.

Academic Editor

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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: (No Response)

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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

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

Reviewer #1: Yes

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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: (No Response)

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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

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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)

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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

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