These nine transcriptome datasets include data from human embryonic stem cell (hESC) and its subsequently differentiated forms (N1, early initiation N2, neural progenitor and N3, early glial-like cell), embryonic day 18 (E18) and postnatal day 7 (P7) mouse brain cortices, and adult mouse brain (AMB), liver (AML), and muscle (AMM). To further investigate the transcriptome dynamics and to better understand the possible roles of unannotated TARs in early neural development, we have analyzed the RNA-seq datasets from embryonic and postnatal mouse brain cortices that we generated recently, as well as seven additional RNA-seq datasets covering both neural and non-neural tissues. The characterization of stage specific unannotated TARs during early brain development could provide clues regarding the roles these unannotated TARs might play in determining neural fate and in regulating neuronal functions. Mammalian neural development is a complex process involving cell division, cell differentiation, cell migration, axon guidance, synaptogenesis, and synaptic plasticity. Our recent study has also detected additional transcripts from intergenic regions and introns in mouse embryonic and neonatal brain cortices. It has been reported that undifferentiated human stem cells have elevated expression of unannotated TARs compared with differentiated neural progenitor cells. Some of the unannotated TARs are large intergenic noncoding RNAs that function in embryonic stem cell pluripotency and cell proliferation, while most unannotated TARs have no known function. In addition, thousands of transcripts from previously unannotated (non-exonic) genomic regions have been reported they are either named TUF (Transcripts of Unknown Function) or unannotated TAR (Transcriptionally Active Region). Another level of transcriptomic complexities has been revealed by extensive analysis of novel splicing variants from known exons. Furthermore, individuals of the same species have transcriptomic differences such as expression variation among humans. It also revealed the transcriptomic complexity during cell differentiation and organ development. Recent high-throughput RNA-seq technologies have provided unprecedented capability to analyze cellular, tissue-specific, or organismal gene activities across a broad spectrum. The Functional Annotation of the Transcriptome of Mammalian Genome (FANTOM) projects (FANTOM 1-4) have demonstrated the complexity of transcriptomes in several aspects, including non-coding RNAs, antisense transcription, regulated retrotransposon expression, and alternative promoter usage, splicing and polyadenylation. The transcriptome and its regulation contribute significantly to eukaryotic diversity in the aforementioned complexity. It is well known that total gene numbers are similar among multicellular eukaryotes, and genome size does not correlate with organism complexity, which differs greatly in terms of development, physiology and behavior among eukaryotes. Our findings provide new insights into potentially novel genes, gene functions and regulatory mechanisms in early brain development. It also suggested potential functional roles for previously unknown transcripts actively expressed in the developing brain cortex. Our results revealed unique global and local landscapes of neural transcriptomes. These functions are the hallmarks of the late embryonic stage cortex, and crucial for synaptogenesis and neural circuit formation. The intronic unannotated expression was found to be strongly associated with genes annotated for neurogenesis, axon guidance, negative regulation of transcription, and neural transmission. We also found an unusually high level of unannotated expression in mouse embryonic brains. We found that the neural and stem cell transcriptomes share global similarity in both gene and chromosomal expression, but are quite different from those of liver or muscle. To investigate the characteristics of neural transcriptomes and possible functions of previously unknown transcripts, we analyzed and compared nine recent RNA-seq datasets corresponding to tissues/organs ranging from stem cell, embryonic brain cortex to adult whole brain. Recent RNA-seq studies unveiled complex transcriptomes with previously unknown transcripts and functions. The transcriptome and its regulation bridge the genome and the phenome.
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