ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2020) 17 1.6 | DOI: 10.1530/ey.17.1.6


To read the full abstract: J Clin Invest. 2020 Feb 3;130(2):641–654. doi: 10.1172/JCI127378. PMID: 31845906.

Congenital pituitary hypoplasia (CPH) is a multifactorial disorder, in which the pituitary has not developed correctly. The underlying mechanisms are mostly unknown, and studies are limited by the lack of appropriate disease models. This work modelled the effect of a novel OTX2 mutation (R127W), encountered in a CPH patient, by using induced pluripotent stem cells (iPSCs) derived from the patient’s leucocytes. Quite intriguingly, the OTX2 mut-iPSCs had an impaired capacity to differentiate into anterior pituitary. This was attributed to deficient capability of hypothalamic OTX2 mut cells to stimulate LHX3 expression in the oral ectoderm cells (giving rise to pituitary progenitor cells) via FGF signaling, which in turn enhanced apoptosis. When the OTX2 mutation was corrected by CRISPR/Cas9 genome editing, the repaired-iPSC again exhibited pituitary differentiation capacity. This study shows that the pituitary and hypothalamus self-organization model in combination with patient-derived iPSCs can be used to analyze the molecular mechanisms of CPH.

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