The existence of a common beta/delta pancreatic endocrine...

The existence of a common beta/delta pancreatic endocrine progenitor was first implied in a mouse study in which it was shown that inactivation of the Pax4 gene, expressed in the early pancreas but later restricted to beta cells, results in the absence of mature beta and delta cells, while alpha cells are not affected (Sosa-Pineda et al. 1997). This was confirmed by a subsequent study showing that Arx and Pax4 transcription factors play opposing roles, with Arx promoting alpha cell lineage commitment, and inhibiting beta and delta fates, while Pax4 inhibits alpha cell fate and promotes beta and delta cell lineage commitment (Collombat et al. 2003).

Single cell RNA-seq (scRNA-seq) studies of the human fetal pancreas imply that the so-called pancreatic endocrine mid progenitor cells (Ma et al. 2023), also known as EP3 (endocrine progenitors at stage 3) (Yu et al. 2021) are the likely endocrine progenitor cell state from which a common beta/delta subgroup of late endocrine progenitors (also known as EP4 progenitors) originate (Yu et al. 2021; Ma et al. 2023).

For a detailed description of pancreatic endocrine mid progenitor cells, please refer to the cell development step “Early progenitor cell of endocrine pancreas produces mid-progenitor cell of endocrine pancreas”.

Pancreatic beta/delta late endocrine progenitor-like cells are characterized by the expression of markers shown in the table below. Only markers identified in at least two studies have been included.

FGF2 and FGF7 are used in protocols for differentiation of both human beta (Yabe et al. 2017) and delta (Chen et al. 2024) cells. In the case of beta cells, they seem to promote proliferation of endocrine progenitors that give rise to beta cells, while at later stages they promote delta cell fate and inhibit beta cell fate (Chen et al. 2024).