Plos iconPlosSep 28, 2026 ~1 min source read

Whole-organ single-cell mapping defines growth dynamics and clonal organization in developing and adult zebrafish livers

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. 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.

Whole-organ single-cell mapping defines growth dynamics and clonal organization in developing and adult zebrafish livers

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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.

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.

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.

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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. 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.

How it works

  • 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.
  • 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...

What to take from it

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.

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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.

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