Differentiation of pituitary cells from iPSCs derived from PBMCs of patients with congenital hypopituitarism

• Grant number: 24/23020-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2025
• End date: December 31, 2025
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Luciani Renata Silveira de Carvalho
• Grantee: Henrique Alves Caffagni
• Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

The pituitary gland is the master gland of the human body, responsible for theproduction and/or secretion of the following hormones: adrenocorticotropic (ACTH),thyroid-stimulating (TSH), growth (GH), follicle-stimulating (FSH), luteinizing (LH),prolactin (PRL), oxytocin, and antidiuretic hormone (ADH). Congenital hypopituitarismis a condition characterized by a deficiency in the production of two or more pituitaryhormones, for which most patients lack a defined molecular diagnosis. Thus, theproduction of induced pluripotent stem cells (iPSCs), a technique developed byTakahashi and Yamanaka in 2007 from somatic cells, has become a promisingapproach for studying hormone-secreting pituitary cells. Accordingly, this study aimsto standardize in a national laboratory the protocol for obtaining pituitary cells in 2Dculture, differentiated from iPSC colonies derived from peripheral blood mononuclearcells (PBMCs) of patients with congenital hypopituitarism, previously established in aninternational laboratory. To confirm the successful differentiation of pituitary cells fromall hormone-producing lineages: corticotropes, thyrotropes, somatotropes,gonadotropes, and lactotropes, we will conduct real-time polymerase chain reaction(RT-PCR) analyses and immunofluorescence for the main secreted hormones. Thus,this study will contribute to expanding knowledge about this condition, potentiallyfacilitating the development of treatments that promote better quality of life for patients. (AU)