Comprehensive transcriptome and methylome analysis delineates the biological basis of hair follicle development and wool-related traits in Merino sheep

Authors: ZHAO, BINGRU - China Agricultural University; LUO, HANPENG - China Agricultural University; HE, JUNMIN - Xinjiang Academy Of Agricultural And Reclamation Science; HUANG, XIXIA - Xinjiang Agricultural University; CHEN, SIQIAN - China Agricultural University; FU, XUEFENG - Xinjiang Academy Of Agricultural And Reclamation Science; ZENG, WEIDAN - Xinjiang Agricultural University; Li, Congjun - Cj; Liu, Ge - George; FANG, LINGZHAO - University Of Edinburgh; ZHANG, SHENGLI - China Agricultural University; TIAN, KECHUAN - Xinjiang Academy Of Agricultural And Reclamation Science

Submitted to: BMC Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/18/2021
Publication Date: 9/9/2021
Citation: Zhao, B., Luo, H., He, J., Huang, X., Chen, S., Fu, X., Zeng, W., Li, C., Liu, G., Fang, L., Zhang, S., Tian, K. 2021. Comprehensive transcriptome and methylome analysis delineates the biological basis of hair follicle development and wool-related traits in Merino sheep. BMC Biology. 19:197. https://doi.org/10.1186/s12915-021-01127-9.
DOI: https://doi.org/10.1186/s12915-021-01127-9

Interpretive Summary: Hair follicle development is important for wool production in livestock. By analyzing multiple omics data, we studied the genetic basis of hair follicle development and detected wool and growth-relevant genes in sheep. These results fill our knowledge gaps and provide the foundation for the future animal breeding program. Farmers, scientist, and policy planners who need improve animal health and production based on genome-enable animal selection will benefit from this study.

Technical Abstract: Background Characterization of the molecular mechanisms underlying hair follicle development is curial for the genetic improvement of wool-relevant economic traits in livestock, and skin-relevant traits in humans. Results Here, to systematically investigate the complexity of hair follicles development, we integrated and analyzed 90 transcriptomic and epigenomic datasets, including mRNA-sequencing (mRNA-seq), lncRNA-seq, circRNA-seq, miRNA-seq, and methylated DNA immunoprecipitation sequencing (MeDIP-seq), across four embryonic stages (E65, E85, E105, and E135) and two postnatal stages (P7 and P30) from skin tissues of 18 Merino sheep. In general, we revealed distinct expression profiles for protein-coding genes (PCGs), miRNA, lncRNA, and circRNA across six developmental stages, and their complex interplays with DNA methylation. The PCGs with stage-specific expression or regulated by stage-specific circRNA, miRNAs and lncRNAs were significantly enriched in epithelium differentiation, hair follicle morphological development, and immune response. The regulatory network and co-expression modules analysis revealed key transcripts that participate in hair follicle morphogenesis. We predicted transcriptional factors (TFs) that participate in hair follicle morphogenesis in a stage-specific manner, including KLF4, LEF1, HOXC13, RBPJ, VDR, RARA, and STAT3. By further integrating results from genome-wide association studies (GWAS, n = 7,135) of five wool-relevant and one growth traits in Merino sheep, we demonstrated that transcripts and co-expression modules with stage-specific expression were significantly associated with such complex traits of economic value. For instance, genes with high and specific expression at E105 were significantly associated with five out of six complex traits. The phenome-wide association studies (PheWAS) further demonstrated that candidate genes of wool and growth-relevant traits (SPHK1, GHR, PPP1R27, CSRP2, EEF1A2, and PTPN1) were significantly associated with dermatological, metabolic, and immune traits in humans, respectively. Conclusions Our findings provide novel insights into the molecular basis of hair follicle morphogenesis in Merino sheep. Our datasets also serve as a valuable resource for functional annotation of the sheep reference genome and the genetic improvement of wool-relevant traits, as well as represent a model for understanding the early development of skin in both livestock and humans.