Epigenetic Regulation of Sebaceous and Meibomian Glands: From Development to Disease
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThis is a manuscript on the epigenetic regulation of sebaceous glands (SG) and meibomian glands (MG). The overall paper is well organized, and the flow is easy to read. In particular, the figures are very helpful for understanding.
However, the content of the manuscript deviates from its title, and there are too many unnecessary descriptions. Unless the following sections are substantially improved, this manuscript should not be accepted.
Section 3, “Overview of Epigenetic Regulatory Mechanisms,” contains descriptions that are not directly related to SG/MG. Even in a review article, approximately one-third of the main text should not be devoted to material that is not directly relevant to the central topic. For many readers, this section likely contains information that is already well known.
Most of Section 5 "Adult SG/MG Homeostasis and Aging" and Section 6 "Common SG and MG Diseases" describe aging and diseasesrelated to SG/MG, but there is no direct discussion of their relationship to epigenetics.
Section 8 "Epigenetic Regulation of PPARγ" provides a detailed description of PPARγ; however, the authors should write a paper on epigenetic regulation.
Most critically, the authors state in Section 8 that the evidence is “Direct evidence linking epigenetic mechanisms to SG biology remains limited.” This sentence could even be interpreted as undermining the very existence or justification of this manuscript.
The following are minor points:
What does “similar maker” in line 91 refer to? There is no specific explanation provided anywhere in the text.
Apocrine glands are not shown in Figure 1A. Are they unrelated to sebaceous glands?
Author Response
Comment 1: Section 3, “Overview of Epigenetic Regulatory Mechanisms,” contains descriptions that are not directly related to SG/MG. Even in a review article, approximately one-third of the main text should not be devoted to material that is not directly relevant to the central topic. For many readers, this section likely contains information that is already well known.
Response 1: We understand the reviewer’s concern. In the manuscript, we emphasized that “In this section, we provide an overview of the principal epigenetic pathways known or likely to regulate the function, development, and homeostasis of SGs and their subtypes.” Although there is currently no direct evidence linking hydroxymethylation, circRNAs, or histone lactylation specifically to SG biology, these epigenetic mechanisms have been implicated in regulating PPARγ, a key regulator of SG development and function. For this reason, we included a brief discussion of these mechanisms to provide conceptual context. However, to better align with the reviewer’s suggestion and avoid overextension, we have removed the relevant sections in the revised manuscript. We hope these revisions adequately address the reviewer’s concern.
Comment 2: Most of Section 5 "Adult SG/MG Homeostasis and Aging" and Section 6 "Common SG and MG Diseases" describe aging and diseasesrelated to SG/MG, but there is no direct discussion of their relationship to epigenetics.
Response 2: We have removed the content related to aging but retained the sections on homeostasis, as multiple epigenetic regulators, such as HDACs and SETD8, are involved in MG/SG proliferation, apoptosis, and progenitor cell maintenance, all of which are critical for gland homeostasis. These roles are clearly described in Section 7 and illustrated in Figure 2.
Comment 3: Section 8 "Epigenetic Regulation of PPARγ" provides a detailed description of PPARγ; however, the authors should write a paper on epigenetic regulation.
Response 3: We have removed the content describing the post-translational modification of PPARγ. The remaining sections focus exclusively on the epigenetic regulation of PPARγ. We have carefully reviewed the revised manuscript to ensure this distinction is clear.
Comment 4: Most critically, the authors state in Section 8 that the evidence is “Direct evidence linking epigenetic mechanisms to SG biology remains limited.” This sentence could even be interpreted as undermining the very existence or justification of this manuscript.
Response 4: We appreciate the reviewer’s opinion. Although this area remains relatively underexplored, a growing number of studies have highlighted the importance of epigenetic regulators in SG/MG biology, as summarized in our manuscript. To our knowledge, a comprehensive review dedicated to this topic has not yet been published. We believe that synthesizing the available evidence may help provide clarity, stimulate further discussion, and encourage additional research in this evolving field. To minimize potential misunderstanding, we have replaced the word “limited” with “emerging” in the revised manuscript.
Comment 5: The following are minor points:
What does “similar maker” in line 91 refer to? There is no specific explanation provided anywhere in the text.
Response 5: By “similar markers,” we mean that both SG and MG stem cells express similar marker genes. We have added the word “genes” in the revised manuscript to improve clarity and avoid potential misunderstanding.
Comment 6: Apocrine glands are not shown in Figure 1A. Are they unrelated to sebaceous glands?
Response 6: Apocrine glands are commonly referred to as sweat glands and are distinct from sebaceous glands in both structure and function.
Reviewer 2 Report
Comments and Suggestions for AuthorsThe manuscript prepared by the authors contains all the necessary information, from the description of the two types of glands, through embryonic development, to the mechanisms of maintaining homeostasis and the aging process. There are some ambiguities that require clarification.
Doubts and elements for improvement:
-Typo in the first paragraph
-In the second paragraph, the authors should also mention the difference in the composition of the secretions produced by the two glands.
-Do the authors believe that paragraph 4 is in the correct place? Shouldn't it be immediately after paragraph 2?
-In the case of sebocytes and adipocytes, it would be useful to know what their life cycles look like. When we look at the life cycles of both cells and compare them under the influence of PPARγ, some are programmed to die, while others can live for several years in cycles of storing and shedding fat. The authors of the manuscript could present a comparison of both cell types and how PPARγ act on them. (Paragraph 8)
-The abbreviation MGD is missing in the abbreviations table
In terms of its scientific context, the article meets all the requirements for a review article. I ask the authors to respond to the review by making appropriate changes to the text.
Author Response
Comment 1: -Typo in the first paragraph
Response 1: We have carefully proofread the first paragraph but did not identify any typographical errors. We would be happy to correct any mistakes if the reviewer could kindly indicate the specific issue.
Comment 2: -In the second paragraph, the authors should also mention the difference in the composition of the secretions produced by the two glands.
Response 2: In the fifth paragraph, we had already noted, with a reference, that “For example, meibum differs in lipid composition from sebum.” We appreciate the reviewer’s suggestion.
Comment 3: -Do the authors believe that paragraph 4 is in the correct place? Shouldn't it be immediately after paragraph 2?
Response 3: Regarding paragraph structure, paragraph 3 introduces the subtypes of sebaceous glands, including the meibomian gland, while paragraph 4 provides more detailed information specifically about the meibomian gland. We therefore believe that the current sequence is reasonable.
Comment 4: -In the case of sebocytes and adipocytes, it would be useful to know what their life cycles look like. When we look at the life cycles of both cells and compare them under the influence of PPARγ, some are programmed to die, while others can live for several years in cycles of storing and shedding fat. The authors of the manuscript could present a comparison of both cell types and how PPARγ act on them. (Paragraph 8)
Response 4: We note that another reviewer suggested focusing more on known epigenetic regulation of SG/MG biological processes. To address this, in the revised manuscript, we removed content with minimal direct evidence linking epigenetic regulation to SG and MG. As the comparison between sebocytes and adipocytes is not closely associated with SG biology, we have chosen not to expand on this in the current manuscript in order to prioritize the other reviewer’s concerns. However, we are actively investigating the role of PPARγ in MG aging and plan to include the reviewer’s suggested content in a future manuscript.
Comment 5: -The abbreviation MGD is missing in the abbreviations table
Response 5: This has been indicated in the table.
Comment 6: In terms of its scientific context, the article meets all the requirements for a review article. I ask the authors to respond to the review by making appropriate changes to the text.
Response 6: We sincerely appreciate the reviewer’s recognition of our manuscript and all the valuable advice provided to improve it.
