Divergent Cell-Type Specific Hypoxia Responses in Human Stem Cell-Derived and Primary Islets.

ABSTRACT:

Background

The success of stem cell-derived islet (SC-islet) therapy for type 1 diabetes is limited by poor graft survival in the hypoxic post-transplantation microenvironment. While the response of SC-islets to chronic hypoxia has been studied, a direct comparison to primary human islets during the acute hypoxic phase has not been performed. Here, we conduct a comparative single-cell transcriptomic and functional analysis of human SC-islets and primary islets exposed to acute hypoxia (1% O₂) over 48 hours.

Results

Our analysis reveals two divergent response patterns. Primary islets exhibit an energy-conserving response, characterized by a β-cell-specific suppression of identity genes (PDX1, MAFA) and pro-apoptotic factors like DDIT3, alongsid

SUBMITTER: Bradley K 

PROVIDER: S-EPMC12330707 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature