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Biology subjects

Lei Chen

Publications and source records attributed to Lei Chen.

2 recordsLinked to original sources

Comparative transcriptome analysis by deep RNA sequencing at early stage of skin pigmentation in goats (Capra hircus)

Although specific genes have been found to be associated with skin pigmentation, the global gene expression profile for the early stage of skin pigmentation and development in mammals is still not well understood. Here we reported a rare natural group of goat (Youzhou dark goat) featuring the dark skin of body including the visible mucous membranes, which may be an exclusive kind of large mammalian species with this special phenotype so far. In the present study, we characterized the 100-day-old fetal skin transcriptome in hyperpigmented (dark-skinned) and wild-type (white-skinned) goats using deep RNA-sequencing. A total of 923,013,870 raw reads from 6 libraries were obtained, and a large number of alternative splicing events were identified in the transcriptome of fetal skin, including the well-known melanogenic genes ASIP, TYRP1, and DCT, which were differentially expressed in the skin between the dark-skinned and white-skinned goats. Further analysis demonstrated that differential genes including ASIP, TYRP1, DCT, WNT2, RAB27A, FZD4, and CREB3L1 were significantly overrepresented in the melanogenesis pathway and several biological process associated with pigmentation. On the other hand, we identified 1616 novel transcripts in goat skin based on the characteristics of their expression level and gene composition. These novel transcripts may represent two distinct groups of nucleic acid molecules. Our findings contribute to the understanding of the characteristics of global gene expression at early stages of skin pigmentation and development, as well as describe an animal model for human diseases associated with pigmentation.

Developmental Biology

Recurrently deregulated lncRNAs associated with HCC tumorigenesis and metastasis revealed by genomic, epigenomic and transcriptomic profiling in paired primary tumor and PVTT samples

Hepatocellular carcinoma (HCC) are highly potent to invade the portal venous system and subsequently develop into the portal vein tumor thrombosis (PVTT). PVTT could induce intrahepatic metastasis, which is closely associated with poor prognosis. A comprehensive systematic characterization of long noncoding RNAs (lncRNAs) associated with HCC metastasis has not been reported. Here, we first assayed 60 clinical samples (matched primary tumor, adjacent normal tissue, and PVTT) from 20 HCC patients using total RNA sequencing. We identified and characterized 8,603 novel lncRNAs from 9.6 billion sequenced reads, indicating specific expression of these lncRNAs in our samples. On the other hand, the expression patterns of 3,212 known and novel recurrently deregulated lncRNAs (in >=20% of our patients) were well correlated with clinical data in a TCGA cohort and published liver cancer data. Some lncRNAs (e.g., RP11-166D19.1/MIR100HG) were shown to be useful as putative biomarkers for prognosis and metastasis. Moreover, matched array data from 60 samples showed that copy number variations (CNVs) and alterations in DNA methylation contributed to the observed recurrent deregulation of 716 lncRNAs. Subsequently, using a coding-noncoding co-expression network, we found that many recurrently deregulated lncRNAs were enriched in clusters of genes related to cell adhesion, immune response, and metabolic processes. Candidate lncRNAs related to metastasis, such as HAND2-AS1, were further validated using RNAi-based loss-of-function assays. The results of our integrative analysis provide a valuable resource regarding functional lncRNAs and novel biomarkers associated with HCC tumorigenesis and metastasis.

Genomics