Tip multipotent pancreatic progenitor cells produce pancr...

Tip multipotent pancreatic progenitor cells produce pancreatic pro-acinar cells (reviewed in Jennings et al. 2015). Pro-acinar cells are still in a precursor state, meaning they are not fully mature but are on the path to becoming fully functional acinar cells (reviewed in Jennings et al. 2015). At the Carnegie stage 19 (CS19, corresponding to post-conception day 46 during post-conception week PCW7 or gestation week GW9) and 21 (CS21, corresponding to post-conception day 51 during PCW8 or GW10) of human embryonic development, the peripheral, GATA4-positive tip cells start to express carboxypeptidase 1 (CPA1). These CPA1-positive cells, considered to be pro-acinar cells, are initially still positive for NKX6-1 (also known as NKX6.1) (Jennings et al. 2013) and SOX9 (Jennings et al. 2013; Villani et al. 2019). Pro-acinar cells gradually lose expression of the latter two proteins so that expression of GATA4 in mature acinar cells is mutually exclusive with expression of NKX6-1 and SOX9 (Jennings et al. 2013). Similarly, based on an immunohistology study of human embryonic development, while at 13.5 weeks of gestation age (GW13) all CPA1-positive cells are also positive for SOX9, the expression of CPA1 and SOX9 is largely mutually exclusive at GW17 (Villani et al. 2019). SOX9-positive cells expressing CPA1 are also positive for PTF1A and PDX1 (Villani et al. 2019). PTF1A continues to play a central role in the maturation and maintenance of acinar cells by regulating the expression of genes involved in digestive enzyme production (reviewed in Jin and Xiang 2019).

Pro-acinar cells are characterized by expression of the following markers:

Based on mouse data, FGF8 and FGF10 stimulate differentiation of acinar cells (Yamaoka et al. 2010), among other potential soluble morphogens (reviewed in Cleveland et al. 2012), but human data is limited.