Brambach Max, Wittmann Jana, Albert Marvin, Julmi Jérôme, Bill Robert, Gilmour Darren
Department of Molecular Life Sciences, University of Zurich, Zürich, Switzerland.
Harvard Medical School, Boston, MA, USA.
Nat Commun. 2025 Jul 25;16(1):6872. doi: 10.1038/s41467-025-62127-9.
Organisms are far greater than the sum of their differentiated cells, as the function of most cell types emerges from their organisation into three-dimensional tissues. Yet, the mechanisms underlying architectural diversity remain poorly understood, partly due to a lack of methods for directly comparing different tissue organisations. Here we establish nuQLOUD, an efficient imaging and computational framework that reduces complex tissues to clouds of nuclear positions, enabling the extraction of cell-type agnostic architectural features. Applying nuQLOUD to whole zebrafish embryos reveals that global tissue diversity can be efficiently reduced to two archetypes, termed 'amorphous' and 'crystalline'. We investigate the role of cadherin cell adhesion molecules in controlling organisational diversity and demonstrate that their expression segregates along tissue-archetypal lines. Targeted perturbations identify N-cadherin as a general driver of the amorphous archetype. This organisation-centric approach provides a way to conceptualise tissue diversification and investigate the underlying mechanisms within a standardised, quantitative framework.
生物体远大于其分化细胞的总和，因为大多数细胞类型的功能源于它们组织成三维组织。然而，结构多样性背后的机制仍知之甚少，部分原因是缺乏直接比较不同组织结构的方法。在这里，我们建立了nuQLOUD，这是一个高效的成像和计算框架，它将复杂组织简化为核位置云，从而能够提取与细胞类型无关的结构特征。将nuQLOUD应用于整个斑马鱼胚胎表明，整体组织多样性可以有效地简化为两种原型，即“无定形”和“晶体”。我们研究了钙粘蛋白细胞粘附分子在控制组织多样性中的作用，并证明它们的表达沿着组织原型线分离。靶向扰动确定N-钙粘蛋白是无定形原型的一般驱动因素。这种以组织为中心的方法提供了一种概念化组织多样化的方式，并在标准化的定量框架内研究其潜在机制。
