Morphogen-driven human iPSCs differentiation in 3D in vitro models of gastrulation is precluded by physical confinement.
Alsehli, H. S.; Roy, E.; Williams, T.; Kuziola, A.; Guo, Y.; Green, J. B.; Gentleman, E.; Danovi, D.
Show abstract
In early human development, gastrulation is tightly associated with lineage specification. The interplay between mechanical forces and biochemical signals during these processes is poorly understood. Here, we dissect the effects of biochemical cues and physical confinement on a 3D in vitro model of gastrulation that uses spheroids formed from human induced pluripotent stem cells (hiPSCs). First, we compare self-renewing versus differentiating media conditions in free-floating cultures, and observe the emergence of organised tri-germ layers. In these unconfined cultures, BMP4 exposure induces polarised expression of SOX17 in conjunction with spheroid elongation. We then physically confine spheroids using PEG-peptide hydrogels and observe dramatically reduced SOX17 expression, albeit rescued if gels that soften over time are used instead. Our study combines high-content imaging, synthetic hydrogels and hiPSCs-derived models of early development to define the drivers causing changes in shape and emergence of germ layers.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Temporal enzymatic treatment to enhance the remodelling of multiple cartilage microtissues into a structurally organised tissue 95%
- Modelling biochemical gradients in vitro to control cell compartmentalization in a microengineered 3D model of the intestinal epithelium 95%
- A Pillar and Perfusion Plate Platform for Robust Human Organoid Culture and Analysis 95%
Similar papers in this journal
- Rapid fabrication of hydrogel micropatterns by projection stereolithography for studying self-organized developmental patterning 95%
- Topological defects govern mesenchymal condensations, offering a morphology-based tool to predict cartilage differentiation 95%
- Increasing salinity of fibrinogen solvent generates stable fibrin hydrogels for cell delivery or tissue engineering 95%
Similar papers in this journal
- Towards a More Objective and High-throughput Spheroid Invasion Assay Quantification Method 94%
- Functional maturation of human neural stem cells in a 3D bioengineered brain model enriched with fetal brain matrix 94%
- In Vitro Proliferation and Long-Term Preservation of Functional Primary Rat Hepatocytes in Cell Fibers 94%
Similar papers in this journal
- Mechanical activation drives tenogenic differentiation of human mesenchymal stem cells in aligned dense collagen hydrogels 96%
- Thiol-ene cross-linked alginate hydrogel encapsulation modulates the extracellular matrix of kidney organoids by reducing abnormal type 1a1 collagen deposition 95%
- Regulation of extracellular matrix assembly and structure by hybrid M1/M2 macrophages 95%
Similar papers in this journal
- Optimising a self-assembling peptide hydrogel as a Matrigel alternative for 3-dimensional mammary epithelial cell culture 96%
- Towards Modular Engineering of Cell Signalling: Topographically-Textured Microparticles Induce Osteogenesis via Activation of Canonical Hedgehog Signalling 95%
- Densified Collagen Tubular Grafts for Human Tissue Replacement and Disease Modelling Applications 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.