Single-Cell Transcriptome Profiling Reveals β Cell Maturation in Stem Cell-Derived Islets after Transplantation.

Area of Science:

• Stem cell biology
• Endocrinology
• Regenerative medicine

Background:

• Human pluripotent stem cells (SC-β cells) offer a potential unlimited source for diabetes cell replacement therapy.
• Current in vitro-generated SC-β cells exhibit functional and transcriptional immaturity compared to native adult β cells.

Purpose of the Study:

• To catalog transcriptional changes in transplanted SC-β cells using single-cell transcriptomic profiling.
• To understand the in vivo maturation process of SC-β cells and other islet cell types.

Main Methods:

• Single-cell transcriptomic profiling of transplanted SC-β cells.
• Analysis of gene expression and protein secretion (insulin, IAPP).

Main Results:

• Transplanted SC-β cells undergo significant transcriptional changes, maturing towards an adult β cell phenotype.
• Increased insulin and IAPP secretion observed post-transplantation.
• Upregulation of key maturation genes (INS, MAFA, CHGB, G6PC2) not found in in vitro differentiation.
• Other differentiated islet cell types (SC-α, SC-EC) also show substantial transcriptional shifts.

Conclusions:

• In vivo transplantation promotes SC-β cell maturation, enhancing function and gene expression.
• This study provides a valuable resource for improving SC-β cell differentiation strategies for diabetes treatment.