Dataset Information

Hydrogel with cell-cell adhesion cues enhances neural regeneration

ABSTRACT: Cell-cell adhesion is crucial for maintaining cell functions and the integrity of tissue structure in organisms. However, cell-cell adhesion cue has not been effectively replicated in biomaterials and cell-cell adhesion associated mechanisms that enhance neural regeneration remained largely unexplored. Here, we present a diffusive N-cadherin functionalized hydrogel system, which provided cell-cell adhesion cue to modulate intercellular communications to significantly promote the formation of active neural network. The dynamic assembly of N-cadherin at cell membrane-hydrogel interface driven by adhered cells occurred at a timescale of minutes, facilitating the reshaping of membrane protrusions to initiate intercellular adherens junctions and modulate long-term cell-cell communications. Focusing on the mechanisms, it is associated with Thrombospondin-1 (THBS-1) mediated neural communication and activation of TGF-β/Smad pathway. Further, this hydrogel system promisingly promoted neurological function recovery in rats following traumatic brain injury. Our study provided the principles of replicating diffusive cell adhesion molecules to mediate cell-cell adhesion in hydrogels, which may have broad applications in the development of engineered biomaterials aimed at modulating cell fates in regeneration of various tissues.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE297157 | GEO | 2025/12/19

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Background: E-cadherin is an adherens junction protein that forms homophilic intercellular contacts in epithelial cells while also interacting with the intracellular cytoskeletal networks. It has roles including establishment and maintenance of cell polarity, differentiation, migration and signalling in cell proliferation pathways. Its downregulation is commonly observed in epithelial tumours and is a hallmark of the epithelial to mesenchymal transition (EMT). Methods: To improve our understanding of how E-cadherin loss contributes to tumorigenicity, we investigated the impact of its elimination from the non-tumorigenic breast cell line MCF10A. We performed cell-based assays and whole genome RNAseq to characterize an isogenic MCF10A cell line that is devoid of CDH1 expression due to an engineered homozygous 4bp deletion in CDH1 exon 11. Results: The E-cadherin-deficient line, MCF10A CDH1-/- showed subtle morphological changes, weaker cell-substrate adhesion, delayed migration, but retained cell-cell contact, contact growth inhibition and anchorage-dependent growth. Within the cytoskeleton, the apical microtubule network in the CDH1-deficient cells lacked the radial pattern of organization present in the MCF10A cells and F-actin formed thicker, more numerous stress fibres in the basal part of the cell. Whole genome RNAseq identified compensatory changes in the genes involved in cell-cell adhesion while genes involved in cell-substrate adhesion, notably ITGA1, COL8A1, COL4A2 and COL12A1, were significantly downregulated. Key EMT markers including CDH2, FN1, VIM and VTN were not upregulated although increased expression of proteolytic matrix metalloprotease and kallikrein genes was observed. Conclusions: Overall, our results demonstrated that E-cadherin loss alone was insufficient to induce an EMT or enhance transforming potential in the non-tumorigenic MCF10A cells but was associated with broad transcriptional changes associated with tissue remodelling. Examination of the impact of E-cadherin (CDH1) loss in an isogenic pair of breast cell lines.

Dataset Information

Hydrogel with cell-cell adhesion cues enhances neural regeneration

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets