Transient matrix remodeling during direct cell-fate reprogramming enables self-assembly of dense neuronal niches
- 1Copenhagen University
Abstract
Native tissues are characterized by high cellular density and continuous reciprocal interactions between cells and the extracellular matrix (ECM), yet recreating these features in vitro remains a major challenge. Current three-dimensional (3D) culture systems typically capture either dense cell-cell interactions or a defined ECM environment, but rarely both. Here, we introduce a strategy that exploits direct fibroblast-to-neuron reprogramming to decouple microenvironment formation from final cell identity. Human dermal fibroblasts were embedded in collagen microgels, where their intrinsic matrix-remodeling capacity drove rapid ECM compaction. Concurrently, the contractile fibroblasts were converted into induced neurons (iN), generating densely packed neuronal microcultures within a remodeled collagen matrix. This approach transforms a defining function of the starting cell type into a mechanism for engineering the microenvironment of the target cell type. The resulting iN-microgels combine high cell density, defined ECM composition, and tunable biophysical properties in a scalable microscale format. By coupling matrix remodeling with cell-fate conversion, our platform establishes a general framework for engineering tissue-like microenvironments and reveals how dynamic 3D extracellular contexts can be integrated into direct cell reprogramming.
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BibTeX
@misc{laurin2026transient,
title = {{Transient matrix remodeling during direct cell-fate reprogramming enables self-assembly of dense neuronal niches}},
author = {K. Laurin and M. Habekost and F. Nilsson and P. Apostolaki and E. B. Roloson and J. Giacomoni and A. Bruzelius and M. F. Wesseler and R. A. Barker and N. B. Larsen and D. Rylander Ottosson and D. J. Mooney and M. Parmar and J. Kajtez},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.27.762125},
url = {https://www.biorxiv.org/content/10.64898/2026.10.27.762125v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Transient matrix remodeling during direct cell-fate reprogramming enables self-assembly of dense neuronal niches
AU - K. Laurin
AU - M. Habekost
AU - F. Nilsson
AU - P. Apostolaki
AU - E. B. Roloson
AU - J. Giacomoni
AU - A. Bruzelius
AU - M. F. Wesseler
AU - R. A. Barker
AU - N. B. Larsen
AU - D. Rylander Ottosson
AU - D. J. Mooney
AU - M. Parmar
AU - J. Kajtez
PY - 2026
DA - 2026/10/27
PB - bioRxiv
DO - 10.64898/2026.10.27.762125
UR - https://www.biorxiv.org/content/10.64898/2026.10.27.762125v1
AB - Native tissues are characterized by high cellular density and continuous reciprocal interactions between cells and the extracellular matrix (ECM), yet recreating these features in vitro remains a major challenge. Current three-dimensional (3D) culture systems typically capture either dense cell-cell interactions or a defined ECM environment, but rarely both. Here, we introduce a strategy that exploits direct fibroblast-to-neuron reprogramming to decouple microenvironment formation from final cell identity. Human dermal fibroblasts were embedded in collagen microgels, where their intrinsic matrix-remodeling capacity drove rapid ECM compaction. Concurrently, the contractile fibroblasts were converted into induced neurons (iN), generating densely packed neuronal microcultures within a remodeled collagen matrix. This approach transforms a defining function of the starting cell type into a mechanism for engineering the microenvironment of the target cell type. The resulting iN-microgels combine high cell density, defined ECM composition, and tunable biophysical properties in a scalable microscale format. By coupling matrix remodeling with cell-fate conversion, our platform establishes a general framework for engineering tissue-like microenvironments and reveals how dynamic 3D extracellular contexts can be integrated into direct cell reprogramming.
ER -