Transcriptomic analysis of human lung development

We decompose the genome-wide expression patterns in 38 embryonic human lung (53-154 days post conception/dpc) into their independent, dominant directions of transcriptomic sample variation in order togain global insight of the developing human lung transcriptome.The characteristic genes and their corresponding bioontologic attribute profile for the latter were identified. We noted the overrepresentation of lung specific attributes (e.g., surfactant proteins) traditionally associated with later developmental stages, and highly ranked attributes (e.g., chemokineimmunologic processes) not previously reported nor immediately apparent in an early lung development context. We defined the 3,223gene union of the characteristic genes of the 3 most dominant sources of variation as the developing lung characteristic subtranscriptome (DLCS). It may be regarded as the minimal gene set describing the essential biology of this process. The developing lung series in this transcriptomic variation perspectiveform a contiguous trajectory with critical time points that both correlate with the 2 traditional morphologic stages overlapping -154 dpc and suggest the existence of 2 novel phases within the pseudoglandular stage. To demonstrate that this characterization is robust, we showed that the model could be used to estimate the gestational age of independent human lung tissue samples with a median absolute error of 5 days, based on the DLCS of their lung profile alone. Repeating this procedure on the homologous transcriptome profiles of developing mouse lung 1419 dpc, we were able to recover their correct developmental chronology.

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Kho AT, Bhattacharya S, Tantisira KG, Carey VJ, Gaedigk R, Leeder JS, Kohane IS, Weiss ST, Mariani TJ