Tankyrase Inhibition Promotes Endocrine Commitment of HPSC-derived Pancreatic Progenitors

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Oct 9

PMID 39384787

Authors

Frankie Poon

Rangarajan Sambathkumar

Roman Korytnikov

Yasaman Aghazadeh

Amanda Oakie

Paraish S Misra

Farida Sarangi

M Cristina Nostro

Affiliations

Soon will be listed here.

Abstract

Human pluripotent stem cells (hPSCs) have the potential to differentiate into various cell types, including pancreatic insulin-producing β cells, which are crucial for developing therapies for diabetes. However, current methods for directing hPSC differentiation towards pancreatic β-like cells are often inefficient and produce cells that do not fully resemble the native counterparts. Here, we report that highly selective tankyrase inhibitors, such as WIKI4, significantly enhances pancreatic differentiation from hPSCs. Our results show that WIKI4 promotes the formation of pancreatic progenitors that give rise to islet-like cells with improved β-like cell frequencies and glucose responsiveness compared to our standard cultures. These findings not only advance our understanding of pancreatic development, but also provide a promising new tool for generating pancreatic cells for research and potential therapeutic applications.

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