AI Insight
Researchers developed a whole-organ expansion microscopy technique (WAO-ExM) that allows visualization of every individual cell in an intact adult zebrafish liver, revealing that the organ contains an average of 1.26 million hepatocytes. They discovered that liver growth occurs through a non-linear pattern with concentrated bursts of cell proliferation, driven by a few hepatocytes undergoing massive clonal expansion rather than uniform growth across all cells. The study also found that tissue architecture and cell proliferation are regulated independently, as disrupting extracellular matrix components affected liver shape without altering total cell numbers.
Why it matters
This technique provides an unprecedented method to track organ growth and cellular organization at single-cell resolution in whole adult organs, which could be applied to study organ development, regeneration, and disease states in other vertebrate organs. The findings challenge previous assumptions about uniform organ growth and may inform approaches to tissue engineering and understanding organ-related diseases.
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by Hsiao-Yuh Roan, Xuejiao Tian, Wei-Chen Chu, Chia-Ming Lee, Hsin Chen, Fiorency Santoso, Chung-Han Wang, Yu-Hsiu Liu, Uday Kumar, He-Yun Hsiao, Chiou-Hwa Yuh, Bi-Chang Chen, Chen-Hui Chen
Vertebrate organs undergo massive growth during the post-embryonic period. Yet, our understanding of how this organ-wide process is organized at single-cell resolution has been limited by an inability to monitor individual cells of different types throughout intact adult organs. Here we establish an integrated workflow of whole adult-organ expansion microscopy (WAO-ExM) that enables in toto single-cell-resolved visualization of every hepatocyte within a complete adult vertebrate liver. Using transgenic reporters to label hepatocyte nuclei, we quantified cell expansion dynamics across the entire post-embryonic growth period, finding that an intact adult liver spanning ~5 mm thickness had an average of 1,265,206 hepatocytes. The data further revealed a non-linear growth regimen in which cell number increased by 538-fold, with a temporally concentrated burst that was not reflective of overall body growth. Integration of lineage tracing with WAO-ExM revealed that cell number increases were driven by a few hepatocytes undergoing drastic clonal expansion at the whole-organ scale. Disruption of extracellular matrix laminins decoupled liver shaping from total cell number increases, suggesting independent regulatory control of tissue architecture and cell proliferation. We also utilized WAO-ExM to monitor diseased livers and other adult organs, including heart and pancreas. Altogether, these findings bridge micrometer-scale cell behaviors with centimeter-scale organ growth, and establish a generalizable platform for adult vertebrate organs to be fully resolved at bona fide single-cell resolution.