Nanolive technology highlights the importance of wnt signaling in organoid self-organization

Cell-cell interactions between embryonic stem cells (ESCs) and trophoblast stem cells (TSCs) play a vital role in tissue formation in developing embryos [1]. The two cell types are known to communicate through the wnt/β-catenin signaling pathway [2], but identifying the mechanism by which signals are transmitted – either via morphogenetic gradients or direct contact – has been elusive to date [3]. Junyent and colleagues investigate this topic in a new article, published in the Proceedings of the National Academy of Sciences of the United States of America, and Nanolive’s technology played a key role in determining their findings.

The researchers used the 3D Cell Explorer (click here) to produce time lapse footage of the dynamics of the interactions that occur between ESCs and TSCs. The images, which were acquired every minute for 12 to 15 h, showed that ESCs contact TSCs using thin finger-like extensions called cytonemes [4]. The high spatial and temporal resolution of the images enabled the authors to quantify the type, number and maximum length of each protrusions.

Through an additional elegant series of experiments using microbeads covered in different wnt ligands the authors were able to determine that this physical contact between ESCs and TSCs is initiated via the secretion of wnt ligands by TSCs. In this video, we can observe ESCs interacting with and grabbing Wnt3-covered microbeads.

These findings have important repercussions for understanding the process of tissue patterning in lab-grown organoids, which play critical roles in R&D drug screening and research in regenerative medicine. This exciting paper can be downloaded here:

(https://www.pnas.org/content/early/2020/03/16/1920837117)

 

  1. Harrison, S. E., Sozen, B., Christodoulou, N., Kyprianou, C. & Zernicka-Goetz, M. Assembly of embryonic and extraembryonic stem cells to mimic embryogenesis in vitro. Science (80-. ). 356, (2017).
  2. Clevers, H., Loh, K. M. & Nusse, R. An integral program for tissue renewal and regeneration: Wnt signaling and stem cell control. Science (80-. ). 346, (2014).
  3. Junyent, S., Garcin, C. L., Szczerkowski, J. L. A., Trieu, T. & Reeves, J. Specialized cytonemes induce self-organization of stem cells. 1–9 (2020) doi:10.1073/pnas.1920837117.
  4. Gradilla, A. C. & Guerrero, I. Cytoneme-mediated cell-to-cell signaling during development. Cell Tissue Res. 352, 59–66 (2013).

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