Fig. 2.

Opportunities in refining the metabolic hierarchy of stem cells and their progeny in the liver. A: general representation of the cell fate determination of the hepatic stem/progenitor cells (HSPCs) to the hepatocytic lineage and their organization is represented. B: to follow the fate of the stem cells and their progeny in the liver upon injury, OPN-iCreERT2;ROSA26RYFP mice could be used. All sorted cells are by definition green, and the green color is therefore not shown to avoid confusion. Reconstitution of the cell fate can be done by sorting yellow fluorescent protein (YFP)⁺ fractions at different time points after injury. C: hypothetically, combination of ALDH activity (here, red substrate) with genetic tracing allows an additional fractionation of the YFP⁺ population. A hypothetical scenario is given, which illustrates a potential bias in ALDH activity depending on cell fate. Red color has been added in cytoplasm for a simplistic view. D: as in C, but now using a mixture of 2 distinct fluorescent-labeled substrates (red and blue), which could even further refine the molecular features of the YFP⁺ sorted cells based on additional subfractionations. Red or blue colors in cytoplasm of cells represent the ALDH^bright populations. ALDH^int and ALDH^dim (for each substrate) are not represented to lighten the figure. With these additional parameters, it will definitively be possible to fractionate further the 3 ALDH^bright populations. ALDH^int, intermediate aldehyde dehydrogenase activity; Aldh^Red, red ALDH activity based on the use of Substrate A-Red; Aldh^Blue, blue ALDH activity based on the use of Substrate B-Blue; Red^Bright, high red ALDH activity; BlueBright: high blue ALDH activity; Red^BrightBlue^Bright, high red and high blue ALDH activities.