We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
ROCKII inhibition promotes the maturation of human pancreatic beta-like cells.
- Authors
Ghazizadeh, Zaniar; Der-I Kao; Amin, Sadaf; Cook, Brandoch; Rao, Sahana; Ting Zhou; Tuo Zhang; Zhaoying Xiang; Kenyon, Reyn; Kaymakcalan, Omer; Chengyang Liu; Evans, Todd; Shuibing Chen
- Abstract
Diabetes is linked to loss of pancreatic beta-cells. Pluripotent stem cells offer a valuable source of human beta-cells for basic studies of their biology and translational applications. However, the signalling pathways that regulate beta-cell development and functional maturation are not fully understood. Here we report a high content chemical screen, revealing that H1152, a ROCK inhibitor, promotes the robust generation of insulin-expressing cells from multiple hPSC lines. The insulin expressing cells obtained after H1152 treatment show increased expression of mature beta cell markers and improved glucose stimulated insulin secretion. Moreover, the H1152-treated beta-like cells show enhanced glucose stimulated insulin secretion and increased capacity to maintain glucose homeostasis after transplantation. Conditional gene knockdown reveals that inhibition of ROCKII promotes the generation and maturation of glucose-responding cells. This study provides a strategy to promote human beta-cell maturation and identifies an unexpected role for the ROCKII pathway in the development and maturation of beta-like cells.
- Subjects
PANCREATIC beta cells; GLUCAGON-like peptide-1 receptor; CELLS; PLURIPOTENT stem cells
- Publication
Nature Communications, 2017, Vol 8, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-017-00129-y