The Maternal Microbiome Programs the MA Epitranscriptome of the Mouse Fetal Brain and Intestine

Overview

Journal Front Cell Dev Biol

Specialty Cell Biology

Date 2022 Jul 25

PMID 35874829

Authors

Zhuoyu Xiao

Sun Liu

Zengguang Li

Jinru Cui

Hailan Wang

Zihan Wang

Qihuan Ren

Laixin Xia

Zhijian Wang

Yuan Li

Affiliations

Soon will be listed here.

Abstract

The microbiome exerts profound effects on fetal development and health, yet the mechanisms underlying remain elusive. N6-methyladenosine (mA) plays important roles in developmental regulation. Although it has been shown that the microbiome affects the mRNA mA modification of the host, it remains unclear whether the maternal microbiome affects mA epitranscriptome of the fetus so as to impact fetal development. Here, we found that loss of the maternal microbiome altered the expression of mA writers and erasers, as well as the mA methylome of the mouse fetal brain and intestine on embryonic day 18. From the mA profiles, we identified 2,655 and 2,252 mA modifications regulated by the maternal microbiome in the fetal brain and intestine, respectively, and we demonstrated that these mA-modified genes were enriched in the neuro/intestinal developmental pathways, such as the Wnt signaling pathway. Finally, we verified that antibiotic treatment mostly recapitulated changes in mA, and we further showed that the loss of heterozygosity of rescued mA levels and the expression changes of some developmental genes in the fetal intestine that resulted from antibiotic treatment. Collectively, our data revealed that the maternal microbiome programs the mA epitranscriptome of the mouse fetal brain and intestine.

Citing Articles

Altered N6-Methyladenosine Modification Patterns and Transcript Profiles Contributes to Cognitive Dysfunction in High-Fat Induced Diabetic Mice.

Cao Z, An Y, Lu Y Int J Mol Sci. 2024; 25(4).

PMID: 38396669 PMC: 10889299. DOI: 10.3390/ijms25041990.

References

Wang Y, Li Y, Yue M, Wang J, Kumar S, Wechsler-Reya R . N-methyladenosine RNA modification regulates embryonic neural stem cell self-renewal through histone modifications. Nat Neurosci. 2018; 21(2):195-206. PMC: 6317335. DOI: 10.1038/s41593-017-0057-1. View

Xiao W, Adhikari S, Dahal U, Chen Y, Hao Y, Sun B . Nuclear m(6)A Reader YTHDC1 Regulates mRNA Splicing. Mol Cell. 2016; 61(4):507-519. DOI: 10.1016/j.molcel.2016.01.012. View

Jabs S, Biton A, Becavin C, Nahori M, Ghozlane A, Pagliuso A . Impact of the gut microbiota on the mA epitranscriptome of mouse cecum and liver. Nat Commun. 2020; 11(1):1344. PMC: 7067863. DOI: 10.1038/s41467-020-15126-x. View

Meyer K, Patil D, Zhou J, Zinoviev A, Skabkin M, Elemento O . 5' UTR m(6)A Promotes Cap-Independent Translation. Cell. 2015; 163(4):999-1010. PMC: 4695625. DOI: 10.1016/j.cell.2015.10.012. View

Liu X, Wang H, Zhao X, Luo Q, Wang Q, Tan K . Arginine methylation of METTL14 promotes RNA N-methyladenosine modification and endoderm differentiation of mouse embryonic stem cells. Nat Commun. 2021; 12(1):3780. PMC: 8213825. DOI: 10.1038/s41467-021-24035-6. View

Huang H, Weng H, Zhou K, Wu T, Zhao B, Sun M . Histone H3 trimethylation at lysine 36 guides mA RNA modification co-transcriptionally. Nature. 2019; 567(7748):414-419. PMC: 6438714. DOI: 10.1038/s41586-019-1016-7. View

Wang X, Lu Z, Gomez A, Hon G, Yue Y, Han D . N6-methyladenosine-dependent regulation of messenger RNA stability. Nature. 2013; 505(7481):117-20. PMC: 3877715. DOI: 10.1038/nature12730. View

Li H, Tong J, Zhu S, Batista P, Duffy E, Zhao J . mA mRNA methylation controls T cell homeostasis by targeting the IL-7/STAT5/SOCS pathways. Nature. 2017; 548(7667):338-342. PMC: 5729908. DOI: 10.1038/nature23450. View

Wang X, Li Y, Chen W, Shi H, Eren A, Morozov A . Transcriptome-wide reprogramming of N-methyladenosine modification by the mouse microbiome. Cell Res. 2018; 29(2):167-170. PMC: 6355850. DOI: 10.1038/s41422-018-0127-2. View

10.

Pertea M, Kim D, Pertea G, Leek J, Salzberg S . Transcript-level expression analysis of RNA-seq experiments with HISAT, StringTie and Ballgown. Nat Protoc. 2016; 11(9):1650-67. PMC: 5032908. DOI: 10.1038/nprot.2016.095. View

11.

Clevers H . Wnt/beta-catenin signaling in development and disease. Cell. 2006; 127(3):469-80. DOI: 10.1016/j.cell.2006.10.018. View

12.

Liao Y, Smyth G, Shi W . featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics. 2013; 30(7):923-30. DOI: 10.1093/bioinformatics/btt656. View

13.

Wu T, Hu E, Xu S, Chen M, Guo P, Dai Z . clusterProfiler 4.0: A universal enrichment tool for interpreting omics data. Innovation (Camb). 2021; 2(3):100141. PMC: 8454663. DOI: 10.1016/j.xinn.2021.100141. View

14.

Zhao B, Wang X, Beadell A, Lu Z, Shi H, Kuuspalu A . mA-dependent maternal mRNA clearance facilitates zebrafish maternal-to-zygotic transition. Nature. 2017; 542(7642):475-478. PMC: 5323276. DOI: 10.1038/nature21355. View

15.

Wu Q, Liang X, Wang K, Lin J, Wang X, Wang P . Intestinal hypoxia-inducible factor 2α regulates lactate levels to shape the gut microbiome and alter thermogenesis. Cell Metab. 2021; 33(10):1988-2003.e7. DOI: 10.1016/j.cmet.2021.07.007. View

16.

Brooks 2nd J, Behrendt C, Ruhn K, Lee S, Raj P, Takahashi J . The microbiota coordinates diurnal rhythms in innate immunity with the circadian clock. Cell. 2021; 184(16):4154-4167.e12. PMC: 8967342. DOI: 10.1016/j.cell.2021.07.001. View

17.

MacDonald B, Tamai K, He X . Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell. 2009; 17(1):9-26. PMC: 2861485. DOI: 10.1016/j.devcel.2009.06.016. View

18.

Geula S, Moshitch-Moshkovitz S, Dominissini D, AlFatah Mansour A, Kol N, Salmon-Divon M . Stem cells. m6A mRNA methylation facilitates resolution of naïve pluripotency toward differentiation. Science. 2015; 347(6225):1002-6. DOI: 10.1126/science.1261417. View

19.

Deng S, Zhang H, Zhu K, Li X, Ye Y, Li R . M6A2Target: a comprehensive database for targets of m6A writers, erasers and readers. Brief Bioinform. 2020; 22(3). DOI: 10.1093/bib/bbaa055. View

20.

Cui X, Wei Z, Zhang L, Liu H, Sun L, Zhang S . Guitar: An R/Bioconductor Package for Gene Annotation Guided Transcriptomic Analysis of RNA-Related Genomic Features. Biomed Res Int. 2016; 2016:8367534. PMC: 4864564. DOI: 10.1155/2016/8367534. View