Abstract
The functions of human brains highly depend on the precise temporal regulation of gene expression, and the temporal brain transcriptome profile across lifespan has been observed. The substantial transcriptome alteration in neural disorders like autism has also been observed and is thought to be important for the pathology. While the cell type composition is known to be variable in brains, it remains unclear how it contributes to the temporal and pathological transcriptome changes in brains. Here, we applied a transcriptome deconvolution procedure to an age series RNA-seq dataset of healthy and autism samples, to quantify the contribution of cell type composition in shaping the temporal and autism pathological transcriptome in human brains. We estimated that composition change was the primary factor of both types of transcriptome changes. On the other hand, genes with substantial composition-independent expression changes were also observed in both cases. Those temporal and autism pathological composition-independent changes, many of which are related to synaptic functions, indicate the important intracellular regulatory changes in human brains in both processes.
Highlights
The functions of human brains highly depend on the precise temporal regulation of gene expression, and the temporal brain transcriptome profile across lifespan has been observed
Different cell types are known to show different spatial-temporal distributions. Such complexity raises the unanswered questions: how much of the age-related molecular change in human brains, or the age-related transcriptome change, is the direct consequence of the cell type composition change? If composition changes contribute to age-related expression changes, what’s the biological meaning of the rest? Similar questions about the molecular changes in neural disorders, including autism, remain opened
To investigate the temporal cell type composition changes across lifespan in human brains, we applied the deconvolution procedure to the age series RNA-seq data set of the human prefrontal cortex (PFC) consisting of 40 postnatal human brain samples aged from two-day old to 61.5 year-old[11]
Summary
The functions of human brains highly depend on the precise temporal regulation of gene expression, and the temporal brain transcriptome profile across lifespan has been observed. We applied a transcriptome deconvolution procedure to an age series RNA-seq dataset of healthy and autism samples, to quantify the contribution of cell type composition in shaping the temporal and autism pathological transcriptome in human brains.
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