CHARACTERIZATION OF X CHROMOSOME INACTIVATION IN HUMAN BLASTOIDS DERIVED FROM INDUCED PLURIPOTENT STEM CELLS

• Grant number: 23/12849-2
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2024
• End date: July 31, 2026
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Lygia da Veiga Pereira
• Grantee: Fabiano Tófoli de Araújo
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 13/08135-2 - CTC - Center for Cell-Based Therapy, AP.CEPID

Abstract

In placental mammals, the X chromosome extra copies inactivation is essential for the viability of female embryos. Despite being well described in mice [1] [2], the process of X chromosome inactivation (XCI) in pre-implantation human embryos still needs to be elucidated [3] [4]. Due to the ethical and technical barriers associated with the use of human embryos in research, the development of a blastocyst model based on stem cells to be used in the study of embryonic dose compensation is desirable. While pluripotent stem cells (PSCs) in primed state (ESC or iPSC) are not suitable for this application, human PSCs in naive state have two active X chromosomes with potential to generate extraembryonic trophoblastic cells and hypoblastic cells [5] . Recently, naive human iPSCs have been used to generate blastoids, three-dimensional structures similar to the human blastocyst. However, the status of the XCI during the conversion and maintenance of these structures has not been analyzed. We propose in this project the establishment of human blastoids from different lineages of human iPSCs to analyze the X chromosome inactivation process during their development. The implementation of human blastoid generation in our laboratory will also benefit groups interested in researching other aspects of human embryonic development and those studying human reproduction.