Progenitor Epithelium

Abstract

SummaryInsulin-producing β cells within the vertebrate fetal pancreas acquire their fate in a step-wise manner. Whereas the intrinsic factors dictating the transcriptional or epigenetic status of pancreatic lineages have been intensely examined, less is known about cell-cell interactions that might constitute a niche for the developing β cell lineage. It is becoming increasingly clear that understanding and recapitulating these steps may instruct in vitro differentiation of embryonic stem cells and/or therapeutic regeneration. Indeed, directed differentiation techniques have improved since transitioning from 2D to 3D cultures, suggesting that the 3D microenvironment in which β cells are born is critical. However, to date, it remains unknown whether the changing architecture of the pancreatic epithelium impacts the fate of cells therein. An emerging challenge in the field is to elucidate how progenitors are allocated during key events, such as the stratification and subsequent resolution of the pre-pancreatic epithelium, as well as the formation of lumens and branches. Here, we assess the progenitor epithelium and examine how it might influence the emergence of pancreatic multipotent progenitors (MPCs), which give rise to β cells and other pancreatic lineages. (J Histochem Cytochem 63:559-574, 2015)

In vivo imaging of emerging endocrine cells reveals a requirement for PI3K-regulated motility in pancreatic islet morphogenesis

“…Similar to our observations in zebrafish, clustering endocrine cells in explants make protrusions and show dynamic morphologies coincident with cluster formation ( Bechard et al, 2016 ; Pauerstein et al, 2015 ; Puri and Hebrok, 2007 ; Kesavan et al, 2014 ). The considerable number of cells induced to cluster in our model creates a situation similar to that in mouse, where large numbers of cells differentiate during the secondary transition ( Marty-Santos and Cleaver, 2015 ). It was difficult, although possible, to visualize filopodial dynamics in naturally arising endocrine cells in zebrafish, as only rare samples showed sufficiently strong fluorescent signal.…”

“…During pancreas development – a process conserved across vertebrate species – morphogenesis is coordinated with the establishment of exocrine, ductal and endocrine islet compartments. In mammalian pancreas, the ‘primary transition’ is characterized by epithelial budding and formation of early primitive endocrine cells, while the definitive endocrine cells arise during a second wave of cell expansion and differentiation called the ‘secondary transition’ ( Marty-Santos and Cleaver, 2015 ). During the secondary transition, endocrine precursors differentiate and emerge from the pre-ductal epithelial plexus and progressively assemble into islets ( Bankaitis et al, 2015 ; Pan and Wright, 2011 ).…”

Cellular and molecular mechanisms coordinating pancreas development

“…The exocrine compartment of the pancreas, which makes up more than 95% of the organ, comprises acinar and ductal cells. Its development commences during epithelial remodeling and branching morphogenesis, at ∼E11.5-12.5 (reviewed by Marty-Santos and Cleaver, 2015). The presence of the mesenchyme is essential for exocrine differentiation due to its production and secretion of pro-exocrine factors such as the TGFβ antagonist follistatin, which induces exocrine differentiation but represses endocrine cell formation (Miralles et al, 1998).…”

Photo-click hydrogels for 3D in situ differentiation of pancreatic progenitors from induced pluripotent stem cells

“…At the PP stage, a plexus of branched tubules was prevalent in the 0.5 kPa gels. These stage-specific morphological differences appeared to resemble early pancreatic organogenesis in vivo, which was characterized by the appearance of a microlumenal network that mature into acinar and ductal networks [ 60 , 61 ]. It has been shown that the pancreatic endoderm interacts with the matrix through integrin signaling, and this interactions may also be influencing polarization and branching of the endoderm epithelium [ 60 , 62 ].…”