Induced pluripotent stem cells (IPSC) to study congenital hypopituitarism

• Grant number: 21/10483-5
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: January 01, 2022
• End date: December 31, 2022
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Luciani Renata Silveira de Carvalho
• Grantee: Juliana Moreira Silva
• Supervisor: Faranak Fattahi
• Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Institution abroad: University of California, San Francisco (UCSF), United States
• Associated to the scholarship: 20/03299-0 - Induced Pluripotent Stem Cells (IPSC) to study Congenital Hypopituitarism, BP.DR

Abstract

The pituitary is a vital gland that produces and secretes hormones related to growth, fertility, lactation, and stress response. Deficiency of one or more pituitary hormones is known as hypopituitarism, the congenital forms of this condition are mainly caused by inactivating mutations in the PROP1 gene, affecting about 52% of familial cases with topical neurohypophysis in the HCFMUSP cohort. With the advancement of recent large-scale sequencing technologies, there has been an exponential increase in the discovery of genes involved in the pathogenesis of congenital hypopituitarism. However, about 82% of cases worldwide and 88% of cases followed at HCFMUSP still remain without a defined molecular diagnosis. Thus, current data show that exonic sequencing is not the most effective tool for defining the molecular diagnosis of congenital hypopituitarism. Alternatives using emerging transcriptional techniques are needed to discover new pathways associated to pituitary development and hormone production, making patient-induced pluripotent cell differentiation into pituitary cells a promising tool for increasing molecular diagnosis and improving treatment of congenital hypopituitarism. (AU)