Transplantable human thyroid organoids generated from embryonic stem cells to rescue hypothyroidism

Abstract

The function of the thyroid gland is to capture iodide in order 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 disorder in humans which is not 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 responsive to changing demands for thyroid hormone. Here we report the first transplantable thyroid organoids derived from human embryonic stem cells capable of restoring plasma thyroid hormone to athyreotic mice as a proof of concept for future therapeutic development.

Single nuclei and spatial transcriptomes suggest a stratification of papillary and anaplastic thyroid cancer cells

“…Fully differentiated and functional thyrocytes express TSHR , TPO and some of them NIS according to snRNA-seq data. The organoids from Romitti et al, albeit functional, also lack expression of NIS in single cell RNA-seq (Figure 5D), while its expression is detectable in bulk RNA-seq (28). This suggests that the lack of NIS expression in our functional thyrocytes profiled with snRNA-seq might be attributable to dropouts rather than true lack of expression.…”

“…Importantly, there was a subset inclusion relationship between these markers with a gradual loss of NIS first, then TPO , TG and finally TSHR (Figure 5B). Hypothesizing that this inclusion relationship could be a fundamental feature of the thyrocyte (de)differentiation process, we measured the same four markers in a recent human scRNA-seq thyroid organoid dataset (28) (Figure 5C). It revealed a gradual gain of TSHR , then TG , TPO and NIS (Figure 5D).…”