Sex-Specific Differences in MicroRNA Expression During Human Fetal Lung Development
Background: Sex-specific differences in fetal lung maturation have been well described; however, little is known about the sex-specific differences in microRNA (miRNA) expression during human fetal lung development. Interestingly, many adult chronic lung diseases also demonstrate sex-specific differ...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.762834/full |
| _version_ | 1819023580066742272 |
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| author | Nancy W. Lin Nancy W. Lin Cuining Liu Cuining Liu Ivana V. Yang Ivana V. Yang Lisa A. Maier Lisa A. Maier Dawn L. DeMeo Cheyret Wood Shuyu Ye Margaret H. Cruse Vong L. Smith Carrie A. Vyhlidal Katerina Kechris Sunita Sharma |
| author_facet | Nancy W. Lin Nancy W. Lin Cuining Liu Cuining Liu Ivana V. Yang Ivana V. Yang Lisa A. Maier Lisa A. Maier Dawn L. DeMeo Cheyret Wood Shuyu Ye Margaret H. Cruse Vong L. Smith Carrie A. Vyhlidal Katerina Kechris Sunita Sharma |
| author_sort | Nancy W. Lin |
| collection | DOAJ |
| description | Background: Sex-specific differences in fetal lung maturation have been well described; however, little is known about the sex-specific differences in microRNA (miRNA) expression during human fetal lung development. Interestingly, many adult chronic lung diseases also demonstrate sex-specific differences in prevalence. The developmental origins of health and disease hypothesis suggests that these sex-specific differences in fetal lung development may influence disease susceptibility later in life. In this study, we performed miRNA sequencing on human fetal lung tissue samples to investigate differential expression of miRNAs between males and females in the pseudoglandular stage of lung development. We hypothesized that differences in miRNA expression are present between sexes in early human lung development and may contribute to the sex-specific differences seen in pulmonary diseases later in life.Methods: RNA was isolated from human fetal lung tissue samples for miRNA sequencing. The count of each miRNA was modeled by sex using negative binomial regression models in DESeq2, adjusting for post-conception age, age2, smoke exposure, batch, and RUV factors. We tested for differential expression of miRNAs by sex, and for the presence of sex-by-age interactions to determine if miRNA expression levels by age were distinct between males and females.Results: miRNA expression profiles were generated on 298 samples (166 males and 132 females). Of the 809 miRNAs expressed in human fetal lung tissue during the pseudoglandular stage of lung development, we identified 93 autosomal miRNAs that were significantly differentially expressed by sex and 129 miRNAs with a sex-specific pattern of miRNA expression across the course of the pseudoglandular period.Conclusion: Our study demonstrates differential expression of numerous autosomal miRNAs between the male and female developing human lung. Additionally, the expression of some miRNAs are modified by age across the pseudoglandular stage in a sex-specific way. Some of these differences in miRNA expression may impact susceptibility to pulmonary disease later in life. Our results suggest that sex-specific miRNA expression during human lung development may be a potential mechanism to explain sex-specific differences in lung development and may impact subsequent disease susceptibility. |
| first_indexed | 2024-12-21T04:41:09Z |
| format | Article |
| id | doaj.art-adba46a740ea4790ae3e9e46bfea5a49 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-21T04:41:09Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-adba46a740ea4790ae3e9e46bfea5a492022-12-21T19:15:41ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-04-011310.3389/fgene.2022.762834762834Sex-Specific Differences in MicroRNA Expression During Human Fetal Lung DevelopmentNancy W. Lin0Nancy W. Lin1Cuining Liu2Cuining Liu3Ivana V. Yang4Ivana V. Yang5Lisa A. Maier6Lisa A. Maier7Dawn L. DeMeo8Cheyret Wood9Shuyu Ye10Margaret H. Cruse11Vong L. Smith12Carrie A. Vyhlidal13Katerina Kechris14Sunita Sharma15Division of Environmental and Occupational Health, National Jewish Health, Denver, CO, United StatesDivision of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, United StatesDivision of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, United StatesDepartment of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado-Denver Anschutz Medical Campus, Aurora, CO, United StatesDivision of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, United StatesDivision of Bioinformatics and Personalized Medicine, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, United StatesDivision of Environmental and Occupational Health, National Jewish Health, Denver, CO, United StatesEnvironmental and Occupational Health, Colorado School of Public Health, Aurora, CO, United StatesChanning Division of Network Medicine, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, United StatesDepartment of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado-Denver Anschutz Medical Campus, Aurora, CO, United StatesDivision of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, United StatesDivision of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, United StatesDivision of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, United StatesChildren’s Mercy Hospital and Clinics, Kansas City, MO, United StatesDepartment of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado-Denver Anschutz Medical Campus, Aurora, CO, United StatesDivision of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, United StatesBackground: Sex-specific differences in fetal lung maturation have been well described; however, little is known about the sex-specific differences in microRNA (miRNA) expression during human fetal lung development. Interestingly, many adult chronic lung diseases also demonstrate sex-specific differences in prevalence. The developmental origins of health and disease hypothesis suggests that these sex-specific differences in fetal lung development may influence disease susceptibility later in life. In this study, we performed miRNA sequencing on human fetal lung tissue samples to investigate differential expression of miRNAs between males and females in the pseudoglandular stage of lung development. We hypothesized that differences in miRNA expression are present between sexes in early human lung development and may contribute to the sex-specific differences seen in pulmonary diseases later in life.Methods: RNA was isolated from human fetal lung tissue samples for miRNA sequencing. The count of each miRNA was modeled by sex using negative binomial regression models in DESeq2, adjusting for post-conception age, age2, smoke exposure, batch, and RUV factors. We tested for differential expression of miRNAs by sex, and for the presence of sex-by-age interactions to determine if miRNA expression levels by age were distinct between males and females.Results: miRNA expression profiles were generated on 298 samples (166 males and 132 females). Of the 809 miRNAs expressed in human fetal lung tissue during the pseudoglandular stage of lung development, we identified 93 autosomal miRNAs that were significantly differentially expressed by sex and 129 miRNAs with a sex-specific pattern of miRNA expression across the course of the pseudoglandular period.Conclusion: Our study demonstrates differential expression of numerous autosomal miRNAs between the male and female developing human lung. Additionally, the expression of some miRNAs are modified by age across the pseudoglandular stage in a sex-specific way. Some of these differences in miRNA expression may impact susceptibility to pulmonary disease later in life. Our results suggest that sex-specific miRNA expression during human lung development may be a potential mechanism to explain sex-specific differences in lung development and may impact subsequent disease susceptibility.https://www.frontiersin.org/articles/10.3389/fgene.2022.762834/fullmicroRNAlung developmentpulmonary diseasesex-specificgene expressionhuman |
| spellingShingle | Nancy W. Lin Nancy W. Lin Cuining Liu Cuining Liu Ivana V. Yang Ivana V. Yang Lisa A. Maier Lisa A. Maier Dawn L. DeMeo Cheyret Wood Shuyu Ye Margaret H. Cruse Vong L. Smith Carrie A. Vyhlidal Katerina Kechris Sunita Sharma Sex-Specific Differences in MicroRNA Expression During Human Fetal Lung Development Frontiers in Genetics microRNA lung development pulmonary disease sex-specific gene expression human |
| title | Sex-Specific Differences in MicroRNA Expression During Human Fetal Lung Development |
| title_full | Sex-Specific Differences in MicroRNA Expression During Human Fetal Lung Development |
| title_fullStr | Sex-Specific Differences in MicroRNA Expression During Human Fetal Lung Development |
| title_full_unstemmed | Sex-Specific Differences in MicroRNA Expression During Human Fetal Lung Development |
| title_short | Sex-Specific Differences in MicroRNA Expression During Human Fetal Lung Development |
| title_sort | sex specific differences in microrna expression during human fetal lung development |
| topic | microRNA lung development pulmonary disease sex-specific gene expression human |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.762834/full |
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