Ensuring reversal of X-chromosome inactivation during naïve iPSC reprogramming
Description: Reprogramming somatic cells into induced pluripotent stem cells (iPSCs) represents a groundbreaking advancement for stem cell biology. However, conventional reprogramming methods produce iPSCs with primed pluripotency traits that fail to fully reset the somatic cell memory. Recent advancements offer naïve iPSCs with superior characteristics, including enhanced pluripotency, reduced somatic epigenetic memory. However, the heterogeneity of epigenetic status of naïve iPSCs, particularly at the level of X-chromosome inactivation (XCI) in female cells, remains a challenge. Here, I propose to investigate XCI dynamics during naïve reprogramming and optimize culture conditions for stable pre-XCI status. The proposed experimental program involves creating a fluorescent reporter system to track XCI reversal during reprogramming and refining media formulations through a small molecule screening. Validation will involve reprogramming primary somatic cells to confirm stable pre-XCI status and pluripotency. The project aims to develop reprogramming techniques that generate high-quality iPSC models for broader application in research and therapy.
Amount: €42,150
Funding type: grant
Funder scheme: FCT
Start date: 2025-03-01
End date: 2029-02-28
Investigator: Francisca Cazaux Mateus
Funded outputs count: 2
Funder award ID: 2024.04039.BDANA
OpenAlex ID: G574245236