Adaptive Landscape Shaped by Core Endogenous Network Coordinates Complex Early Progenitor Fate Commitments in...

Area of Science:

• Developmental Biology
• Cell Biology
• Genetics

Background:

• The classical pancreatic development hierarchy is challenged by progenitor heterogeneity.
• Early pancreatic progenitor fate commitments from multipotency to unipotency are not well-characterized.

Purpose of the Study:

• To mechanistically understand complex pancreatic progenitor fate commitments.
• To construct and quantify an endogenous network for pancreatic lineage decisions.

Main Methods:

• Dynamic modeling of genetic regulations to quantify network properties.
• Analysis of single-cell RNA sequencing (scRNA-seq) data for validation.

Main Results:

• A complex developmental landscape for pancreatic lineage decisions was revealed.
• Previously unrecognized progenitors (TiP, TrP, LEP, AciP/AciP2) were predicted.
• Roles of predicted progenitors in endocrine, acinar, and ductal lineage maturation were identified.

Conclusions:

• A redefined hierarchy of early pancreatic progenitor fate commitment was established.
• The study provides a detailed mechanistic understanding of pancreatic development.
• Predicted progenitor cell fates were validated using scRNA-seq data.