PDX1LOW MAFALOW β-cells contribute to islet function and insulin release.
IF: 17.694
Cited by: 41


Transcriptionally mature and immature β-cells co-exist within the adult islet. How such diversity contributes to insulin release remains poorly understood. Here we show that subtle differences in β-cell maturity, defined using PDX1 and MAFA expression, contribute to islet operation. Functional mapping of rodent and human islets containing proportionally more PDX1HIGH and MAFAHIGH β-cells reveals defects in metabolism, ionic fluxes and insulin secretion. At the transcriptomic level, the presence of increased numbers of PDX1HIGH and MAFAHIGH β-cells leads to dysregulation of gene pathways involved in metabolic processes. Using a chemogenetic disruption strategy, differences in PDX1 and MAFA expression are shown to depend on islet Ca2+ signaling patterns. During metabolic stress, islet function can be restored by redressing the balance between PDX1 and MAFA levels across the β-cell population. Thus, preserving heterogeneity in PDX1 and MAFA expression, and more widely in β-cell maturity, might be important for the maintenance of islet function.


Gene Expression
Spatial Transcriptomics

MeSH terms

Cells, Cultured
Diabetes Mellitus, Type 2
Gene Knock-In Techniques
Homeodomain Proteins
Insulin Secretion
Insulin-Secreting Cells
Maf Transcription Factors, Large
Mice, Transgenic
Models, Animal
Primary Cell Culture


Nasteska, Daniela
Fine, Nicholas H F
Ashford, Fiona B
Cuozzo, Federica
Viloria, Katrina
Smith, Gabrielle
Dahir, Aisha
Dawson, Peter W J
Lai, Yu-Chiang
Bastidas-Ponce, Aimée
Bakhti, Mostafa
Rutter, Guy A
Fiancette, Remi
Nano, Rita
Piemonti, Lorenzo
Lickert, Heiko
Zhou, Qiao
Akerman, Ildem
Hodson, David J

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