Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly ‘housekeeping’, whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.
In the FANTOM5 project, transcription initiation events across the human and mouse genomes were mapped at a single base-pair resolution and their frequencies were monitored by CAGE (Cap Analysis of Gene Expression) coupled with single-molecule sequencing. Approximately three thousands of samples, consisting of a variety of primary cells, tissues, cell lines, and time series samples during cell activation and development, were subjected to a uniform pipeline of CAGE data production. The analysis pipeline started by measuring RNA extracts to assess their quality, and continued to CAGE library production by using a robotic or a manual workflow, single molecule sequencing, and computational processing to generate frequencies of transcription initiation. Resulting data represents the consequence of transcriptional regulation in each analyzed state of mammalian cells. Non-overlapping peaks over the CAGE profiles, approximately 200,000 and 150,000 peaks for the human and mouse genomes, were identified and annotated to provide precise location of known promoters as well as novel ones, and to quantify their activities.
The present study examined infants' brain activity in response to upright and inverted faces using near infrared spectroscopy (NIRS), which can non-invasively record hemodynamic changes of the brain. NIRS is particularly useful for recording in infants, since recordings can be made, even while the infants are awake, without fixing their body and brain. For this objective, we used newly developed sensor probes of NIRS for recording in infants. We measured changes in cerebral oxygenation in 10 5-8-month-olds' left and right lateral areas while they were looking at upright and inverted faces. The results are summarized as follows: (1) the concentration of oxyhemoglobin (oxy-Hb) and total hemoglobin (total-Hb) increased significantly in the right lateral area during the upright face condition, (2) the concentration of total-Hb in the right lateral area differed significantly between the upright and inverted conditions, (3) hemodynamic changes were maximal in the temporal region, probably in the superior temporal sulcus (STS) in both hemispheres, and (4) the right hemisphere seems to be more important for recognizing upright faces. This is the first evidence showing that there is an inter-hemispheric difference on the effect of face inversion in the infant brain using a hemodynamic method.
The objective of the present study was to determine whether a developmental difference occurs in brain activity when infants look at frontal and profile views using near-infrared spectroscopy (NIRS), which is an optical imaging technique used to measure changes in the concentrations of oxyhemoglobin (oxy-Hb), deoxyhemoglobin (deoxy-Hb), and total hemoglobin (total-Hb). For this objective, we compared NIRS results in two age groups, 5- and 8-month-old infants, while they were looking at frontal views, profile views, and objects. We found that the concentration of oxy-Hb and total-Hb in the 5-month-old group increased for only frontal views in the right temporal regions. In contrast, the concentration of oxy-Hb and total-Hb in the 8-month-old group increased for both frontal and profile views in the right temporal regions. Therefore, the present study indicated that the right hemisphere was dominant for the perception of profile views as well as frontal views. In addition, the most important and interesting finding was that the infants' brain activity of the face area would become view-invariant at the age of 8 months but not at 5 months. The developmental period for view-invariant face recognition has been discussed in previous psychological studies, but this is the first objective study to confirm that the period is between 5- and 8-months by measuring the blood flow in the brain using NIRS.
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