Early progenitor cell number as organ size determinant: pancreas

Developmental biology is the gold mine of stem cell biology. A pioneer, but elegant quantitative cell biology paper was published in Nature advance online publication on 28, January 2007 by U.S. researchers Stanger, Tanaka, Melton along developmental lines.
Based on the strict regulation of vertebrate development it was thought that extrinsic or systemic signals, growth factors and apoptotic factors have a decisive role in determining and restoring the final size and shape of an organ even after big cellular loss during embryogenesis and regeneration. Extrinsic signals regulate size in many vertebrate tissues, including blood, liver, muscle and the central nervous system by controlling cell proliferation or by modulating cell death. Not in mice’s pancreas! Two different methods—cell ablation and tissue complementation—were used to perturb precursor cell number during the earliest stages of pancreatic and liver development. Liver was chosen because of its close developmental relationship to the pancreas. Transgenic mice strains were used, in which pancreatic and hepatic progenitor cell number can be regulated, ablated, restored. To assess the capacity for compensatory growth, embryos were generated in which many, but not all, progenitor cells were ablated.

Setting aside the complicated (really) technological details it was showed, that “compensatory growth during pancreas development is either quite limited or does not occur at all. Thus, embryonic progenitor cells represent a critical and limiting determinant of pancreas size. These observations support the notion that pancreatic progenitor cell growth follows an intrinsic or autonomous programme, one that does not aim to achieve a certain final size for the whole organ. The liver, by contrast, exhibits robust and precise compensatory growth in response to cell ablation. Overall, these results suggest that the size of some organs (including the pancreas) may be relatively fixed early in development and that growth factors may have a limited or more permissive role in determining final size.” Link