Modeling of embryonic tumor of the central nervous system from neuroprogenitor cells derived from human pluripotent stem cells

• Grant number: 18/23337-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2019
• End date: July 28, 2021
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Oswaldo Keith Okamoto
• Grantee: Vitória Alves de Lima
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Certain Central Nervous System (CNS) tumors, such as medulloblastoma, are caused by genetic changes in stem cells or neuronal progenitor cells, even during the embryonic stage of development. Previous studies of our group identified an abnormal expression of pluripotency factors in medulloblastoma. One such factor is OCT4A, one of the five isoforms generated by alternative splicing of the POU5F1 gene. OCT4A is normally expressed in early stages of embryonic development, consisting of one of the major factors regulating pluripotency and self-renewal of embryonic stem cells (CTE). Expression of OCT4A decays from the differentiation of CTE and is not found in progenitor cells and in terminally differentiated cells. In medulloblastoma, however, we detected a high and aberrant expression of OCT4A, which contributes to tumor aggressiveness and is related to the low survival of the affected patients. Thus, in the present project, we intend to study the consequences of OCT4A expression in human neuronal stem cells to verify if the aberrant expression of this pluripotency factor can exert oncogenic effects capable of favoring neoplastic transformation of CNS stem/progenitor cells. We propose to investigate this issue through the development of an experimental model characterized by conditioned overexpression of OCT4A in human neural stem cells derived from CTE and functional study focused on tumorigenic properties.