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Science Advances

Science Advances

IF: 11.7
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Human expandable pancreatic progenitor–derived β cells ameliorate diabetes

Published:23 February 2022 DOI: 10.1126/sciadv.abk1826 PMID: 35196077
Xiaojie Ma, Yunkun Lu, Ziyu Zhou, Qin Li, Xi Chen, Weiyun Wang, Yan Jin, Zhensheng Hu, Guo Chen, Qian Deng, Weina Shang, Hao Wang, Hongxing Fu, Xiangwei He, Xin-Hua Feng, Saiyong Zhu

Abstract

An unlimited source of human pancreatic β cells is in high demand. Even with recent advances in pancreatic differentiation from human pluripotent stem cells, major hurdles remain in large-scale and cost-effective production of functional β cells. Here, through chemical screening, we demonstrate that the bromodomain and extraterminal domain (BET) inhibitor I-BET151 can robustly promote the expansion of PDX1+NKX6.1+ pancreatic progenitors (PPs). These expandable PPs (ePPs) maintain pancreatic progenitor cell status in the long term and can efficiently differentiate into functional pancreatic β (ePP-β) cells. Notably, transplantation of ePP-β cells rapidly ameliorated diabetes in mice, suggesting strong potential for cell replacement therapy. Mechanistically, I-BET151 activates Notch signaling and promotes the expression of key PP-associated genes, underscoring the importance of epigenetic and transcriptional modulations for lineage-specific progenitor self-renewal. In summary, our studies achieve the long-term goal of robust expansion of PPs and represent a substantial step toward unlimited supplies of functional β cells for biomedical research and regenerative medicine.

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Materials
Procduct Name CAS Molecular Formula Supplier Price
Forskolin 66575-29-9 C22H34O7 536 suppliers $12.00-$1786.00
Forskolin 66575-29-9 C22H34O7 536 suppliers $12.00-$1786.00
Forskolin 66575-29-9 C22H34O7 536 suppliers $12.00-$1786.00
Forskolin 66575-29-9 C22H34O7 536 suppliers $12.00-$1786.00
CHIR-99021 252917-06-9 C22H18Cl2N8 339 suppliers $28.00-$4401.00
CHIR-99021 252917-06-9 C22H18Cl2N8 339 suppliers $28.00-$4401.00
CHIR-99021 252917-06-9 C22H18Cl2N8 339 suppliers $28.00-$4401.00
CHIR-99021 252917-06-9 C22H18Cl2N8 339 suppliers $28.00-$4401.00
ALK5 inhibitor II 446859-33-2 C17H13N5 242 suppliers $10.00-$4788.00
ALK5 inhibitor II 446859-33-2 C17H13N5 242 suppliers $10.00-$4788.00

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