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Single-cell RNA-Seq of mouse thyroid organoid

ABSTRACT: Single-cell RNA-Seq of mouse thyroid organoid

PROVIDER: PRJNA687677 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13302214_1.fastq.gz	Fastqsanger.gz
	SRR13302214_2.fastq.gz	Fastqsanger.gz
	SRR13302215_1.fastq.gz	Fastqsanger.gz
	SRR13302215_2.fastq.gz	Fastqsanger.gz

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Single-cell RNA-Seq of mouse thyroid organoid

Project description:Single-cell RNA-Seq of mouse thyroid organoid

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Single-cell RNA-Seq of mouse thyroid organoid

Project description:The thyroid gland regulates metabolism and growth via secretion of thyroid hormone by thyroid follicular cells (TFCs). Loss of TFCs, by cellular dysfunction, autoimmune destruction or surgical resection, underlies hypothyroidism. Recovery of thyroid hormone levels by transplantation of mature TFCs derived from stem cells in vitro holds great therapeutic promise. However, the utilization of in vitro derived tissue for regenerative medicine is restricted by the efficiency of differentiation protocols to generate mature organoids. Here, to improve the differentiation efficiency for thyroid organoids, we utilized single-cell RNA-Seq to chart the molecular steps undertaken by individual cells during the in vitro transformation of mouse embryonic stem cells to TFCs. Our single-cell atlas of mouse organoid systematically and comprehensively identifies, for the first time, the cell-types generated during production of thyroid organoids. Using pseudotime analysis, we identify molecular pathways that regulate thyroid maturation in vitro. Our study highlights the potential of single-cell molecular characterization in understanding and improving thyroid maturation, and paves the way for identification of therapeutic targets against thyroid disorders.

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Project description:The function of the thyroid gland is to metabolize iodide to synthesize hormones that act on almost all tissues and are essential for normal growth and metabolism. Low plasma levels of thyroid hormones lead to hypothyroidism, which is one of the most common diseases in the general population and cannot be always satisfactorily treated by lifelong hormone replacement. Therefore, in addition to the lack of in vitro tractable models to study human thyroid development, differentiation and maturation, there is a need for new therapeutic approaches that involve replacement of thyroid tissue to better control hormone balance. Here we report the first model of thyroid organoids derived from human embryonic stem cells that produce thyroid hormones in vitro and are capable of restoring plasma thyroid hormone levels when transplanted into athyreotic mice.

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Project description:The thyroid maintains systemic homeostasis by regulating serum thyroid hormone concentrations. Here we report the establishment of adult stem cell-derived three-dimensional (3D) organoids representing murine and human thyroid follicular cells (TFCs). The TFC organoids (TFCO) harbour the complete machinery of hormone production as visualised by the presence of colloid in the lumen and by the presence of essential transporters and enzymes in the polarised epithelial cells that surround a central lumen. Both the established murine as human thyroid organoids express canonical thyroid markers PAX8 and NKX2.1, while the thyroid hormone precursor thyroglobulin is expressed at comparable levels to tissue. Single cell RNA sequencing and transmission electron microscopy confirm that TFCOs phenocopy primary thyroid tissue. Thyroid hormones are readily detectable in conditioned medium of human TFCOs.

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