A molecular view of the normal human thyroid structure and function reconstructed from its reference transcriptome map

Abstract

BackgroundThe thyroid is the earliest endocrine structure to appear during human development, and thyroid hormones are necessary for proper organism development, in particular for the nervous system and heart, normal growth and skeletal maturation. To date a quantitative, validated transcriptional atlas of the whole normal human thyroid does not exist and the availability of a detailed expression map might be an excellent occasion to investigate the many features of the thyroid transcriptome.ResultsWe present a view at the molecular level of the normal human thyroid histology and physiology obtained by a systematic meta-analysis of all the available gene expression profiles for the whole organ. A quantitative transcriptome reference map was generated by using the TRAM (Transcriptome Mapper) software able to combine, normalize and integrate a total of 35 suitable datasets from different sources thus providing a typical reference expression value for each of the 27,275 known, mapped transcripts obtained. The experimental in vitro validation of data was performed by “Real-Time” reverse transcription polymerase chain reaction showing an excellent correlation coefficient (r = 0.93) with data obtained in silico.ConclusionsOur study provides a quantitative global reference portrait of gene expression in the normal human thyroid and highlights differential expression between normal human thyroid and a pool of non-thyroid tissues useful for modeling correlations between thyroidal gene expression and specific thyroid functions and diseases. The experimental in vitro validation supports the possible usefulness of the human thyroid transcriptome map as a reference for molecular studies of the physiology and pathology of this organ.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-017-4049-z) contains supplementary material, which is available to authorized users.

Identification of <b><i>Transient Receptor Potential Channel 4-Associated Protein</i></b> as a Novel Candidate Gene Causing Congenital Primary Hypothyroidism

“…2a). Specific thyroid expression of TRPC4AP has been previously also detected by exploration of the human thyroid transcriptome [19]. Pathway analyses provided evidence that TRPC4AP is linked to significant transcription factors and peptides which are involved in anlage, proliferation, migration, growth, organization, differentiation, and survival of the thyroid gland and thyroid hormone synthesis ( Fig.…”

Dataset of differential gene expression between total normal human thyroid and histologically normal thyroid adjacent to papillary thyroid carcinoma

“…In the histologically normal thyroid adjacent to papillary thyroid carcinoma transcriptome map, the search for housekeeping genes with the described criteria ( Methods section ) retrieved 414 loci, including the known genes RPL41 , and TG , encoding for ribosomal protein L41 and thyroglobulin, respectively, having low standard deviation (SD), the highest expression values and a high number of data points (n=40) ( Table 5 ). This search did not give the same results of total normal thyroid transcriptome map (see Table 4 [1] ). The two transcriptome maps have in common only seven genes: ACTG1 , BLOC1S2 , DIABLO , OCIAD2 , GTPBP6 , EIF2B2 , AKR1B1 .…”

“…The 35 datasets of the total thyroid were already used in Ref. [1] . Sample identifiers (GEO and EBI ID numbers) and main sample features are listed in the Supplementary Table 1 .…”

“…The differential transcriptome map was performed integrating 35 datasets from total normal human thyroid [1] and 40 datasets from histologically normal thyroid adjacent to papillary thyroid carcinoma. The 35 datasets included in the Pool A folder provided reference gene expression values for 25,574 loci coming from 947,816 data points (data from Ref.…”

“…The 35 datasets included in the Pool A folder provided reference gene expression values for 25,574 loci coming from 947,816 data points (data from Ref. [1] updated after the analysis with TRAM 1.3 software version), the 40 datasets included in the Pool B folder provided reference gene expression values for 24,699 loci ( Supplementary Table 2 ) coming from 1,917,840 data points, and the differential transcriptome map obtained provided reference gene expression values for 24,699 loci ( Supplementary Table 3 ) common to both pools ( Fig. 1 ).…”