Differentiation of stem cells into thyroid tissue

An ex vivo or in vitro method for producing a mature thyroid follicular epithelial cell comprising:

• a) contacting an endodermal cell with a thyroid lineage culture medium to differentiate the endodermal cell into the thyroid lineage without exogenously delivered nucleic acid sequences resulting in the forced over-expression of the Nkx2-1 protein and the Pax8 protein in the endodermal cell, thereby producing a Nkx2.1+ and Pax8+ thyroid progenitor cell, wherein the thyroid lineage culture medium comprises:
• i) bone morphogenetic protein 4 (BMP4), and
• ii) fibroblast growth factor 2 (basic) (FGF2), and
• wherein the thyroid lineage culture medium does not contain:
• iii) Wingless-Type MMTV Integration Site Family protein, member 3A, (Wnt3A),
• iv) fibroblast Growth Factor 10 ((FGF10),
• v) keratinocyte Growth Factor (KGF), and
• vi) epidermal growth factor (EGF),
• b) isolating and culturing the Nkx2-1+/Pax8+ thyroid progenitor cell of step (a) in a differentiation medium comprising fibroblast growth factor 2 (basic) (FGF2) for a time sufficient to permit differentiation of the Nkx2-1+/Pax8+ thyroid progenitor cell along the thyroid lineage;
• and
• c) culturing the further differentiated cell produced in step (b) in a maturation medium comprising dexamethasone and thyroid stimulating hormone (TSH), under conditions and for a time sufficient to produce a Nkx2-1+/Pax8+ co-expressing cell that also expresses early and mature thyroid markers:
• thyroglobulin (Tg+), thyroid stimulating hormone receptor (Tsh+), sodium iodine symporter (Nis+), and thyroid peroxidase (Tpo+),
• thereby producing a mature thyroid follicular epithelial cell.