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. 2021 May 21:12:579800.
doi: 10.3389/fgene.2021.579800. eCollection 2021.

Whole-Transcriptome Analysis of Yak and Cattle Heart Tissues Reveals Regulatory Pathways Associated With High-Altitude Adaptation

Hui Wang  1   2 , Jincheng Zhong  1   2 , Jikun Wang  1   2 , Zhixin Chai  1   2 , Chengfu Zhang  3 , Jinwei Xin  3 , Jiabo Wang  1   2 , Xin Cai  1   2 , Zhijuan Wu  1   2 , Qiumei Ji  3
Affiliations

Whole-Transcriptome Analysis of Yak and Cattle Heart Tissues Reveals Regulatory Pathways Associated With High-Altitude Adaptation

Hui Wang et al. Front Genet. .

Abstract

Background: The yak (Bos grunniens) is an important livestock species that can survive the extremely cold, harsh, and oxygen-poor conditions of the Qinghai-Tibetan Plateau and provide meat, milk, and transportation for the Tibetans living there. However, the regulatory network that drive this hypoxic adaptation remain elusive.

Results: The heart tissues from LeiRoqi (LWQY) yak and their related cattle (Bos Taurus) breeds, which are two native cattle breeds located in high altitude (HAC) and low altitude (LAC) regions, respectively, were collected for RNA sequencing. A total of 178 co-differentially expressed protein-coding transcripts (co-DETs) were discovered in each of the LAC-vs-LWQY and LAC-vs-HAC comparison groups, including NFATC2, NFATC1, ENPP2, ACSL4, BAD, and many other genes whose functions were reported to be associated with the immune-system, endocrine-system, and lipid metabolism. Two and 230 lncRNA transcripts were differentially expressed in the LAC-vs-LWQY and LAC-vs-HAC comparisons' respectively, but no lncRNA transcripts that were co-differentially expressed. Among the 58 miRNAs that were co-differentially expressed, 18 were up-regulated and 40 were down-regulated. In addition, 640 (501 up-regulated and 139 down-regulated) and 152 (152 up-regulated and one down-regulated) circRNAs showed differential expression in LAC-vs-LWQY and LAC-vs-HAC comparison groups, respectively, and 53 up-regulated co-differentially expressed circRNAs were shared. Multiple co-DETs, which are the targets of miRNAs/lncRNAs, are significantly enriched in high-altitude adaptation related processes, such as, T cell receptor signaling, VEGF signaling, and cAMP signaling. A competing endogenous RNA (ceRNA) network was constructed by integrating the competing relationships among co-differentially expressed mRNAs, miRNAs, lncRNAs and circRNAs. Furthermore, the hypoxic adaptation related ceRNA network was constructed, and the six mRNAs (MAPKAPK3, PXN, NFATC2, ATP7A, DIAPH1, and F2R), the eight miRNAs (including miR-195), and 15 circRNAs (including novel-circ-017096 and novel-circ-018073) are proposed as novel and promising candidates for regulation of hypoxic adaptation in the heart.

Conclusion: In conclusion, the data recorded in the present study provides new insights into the molecular network of high-altitude adaptation along with more detailed information of protein-coding transcripts and non-coding transcripts involved in this physiological process, the detailed mechanisms behind how these transcripts "crosstalk" with each other during the plateau adaptation are worthy of future research efforts.

Keywords: cattle; ceRNA network; co-differentially expressed transcripts; hypoxic adaptation; whole-transcriptome; yak.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
The distribution of alternative splicing events in the HAC and LAC groups (A), and the differentially expressed mRNA transcripts (B), lncRNA transcripts (C), miRNA transcripts (D), and circRNA transcripts (E) in the LAC-vs-LWQY and LAC-vs-HAC comparison groups. “SE” is short for “skipped exon,” “A3SS” is short for “alternative 3′ splice site,” “A5SS” is short for “alternative 5′ splice site,” “MXE” is short for “mutually exclusive exon,” “RI” is short for “retained intron,” “HAC” is short for “high-altitude cattle,” “LAC” is short for “low-altitude cattle,” “LWQY” is short for “LeiRoqi yak.”
FIGURE 2
FIGURE 2
Kyoto Encyclopedia of Genes and Genomes pathway assignments for the 178 differentially co-expressed protein-coding transcripts between the LAC-vs-LWQY and LAC-vs-HAC comparison groups. “KEGG” is short for “Kyoto Encyclopedia of Genes and Genomes.”
FIGURE 3
FIGURE 3
The protein-coding and lncRNA transcripts characteristics in the yak and cattle hearts. (A,B) FPKM (Fragment Per Kilobase of transcript per Million mapped reads) for protein-coding and lncRNA transcripts in LWQY (A) and cattle (B). (C,D) The distribution of read lengths for protein-coding and lncRNA transcripts in LWQY (C) and cattle (D). (E,F) The proportions of exons per transcript for protein-coding and lncRNA transcripts in LWQY (E) and cattle (F). (G,H) The GC contents of protein-coding and lncRNA transcripts in LWQY (G) and cattle (H).
FIGURE 4
FIGURE 4
Kyoto Encyclopedia of Genes and Genomes pathway analysis of the 125 differentially co-expressed genes targeted by the 58 differentially co-expressed miRNAs.
FIGURE 5
FIGURE 5
An overview of the competing endogenous RNA (ceRNA) network (A) and the predicted hypoxic ceRNA network (B). The red squares, green circles, and yellow triangles indicate co-DETs, co-DEMs, and co-DECs, respectively. The dark blue rectangle indicates the differentially expressed lncRNA transcripts in the LAC-vs-LWQY comparison group.
FIGURE 6
FIGURE 6
Validation of differentially expressed genes. (A) The RNA-seq results of the transcripts. (B) the RT-qPCR results of the transcripts.
See this image and copyright information in PMC

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