The effect of substrate topography on direct reprogramming of fibroblasts to induced neurons
Open accessAbstract
Cellular reprogramming holds tremendous potential for cell therapy and regenerative medicine. Recently, fibroblasts have been directly converted into induced neurons (iNs) by overexpression of the neuronal transcription factors Ascl1, Brn2 and Myt1L. Hypothesizing that cell-topography interactions could influence the fibroblast-to-neuron reprogramming process, we investigated the effects of various topographies on iNs produced by direct reprogramming. Final iN purity and conversion efficiency were increased on micrograting substrates. Neurite branching was increased on microposts and decreased on microgratings, with a simplified dendritic arbor characterized by the reduction of MAP2(+) neurites. Neurite outgrowth increased significantly on various topographies. DNA microarray analysis detected 20 differentially expressed genes in iNs reprogrammed on smooth versus microgratings, and quantitative PCR (qPCR) confirmed the upregulation of Vip and downregulation of Thy1 and Bmp5 on microgratings. Electrophysiology and calcium imaging verified the functionality of these iNs. This study demonstrates the potential of applying topographical cues to optimize cellular reprogramming.
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BMDMs oriented along the grooved titanium surfaces, mostly parallel to the groove direction.
“bone marrow derived macrophages aligned along the grooved surface topographies, generally in the direction parallel to the grooves”
From Micro- and Nanopatterned Topographical Cues for Regulating Macrophage Cell Shape and Phenotype (2015) · cites this paper as [37]
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References 36 · Cited by 102
- Authors
- Kulangara, K., Adler, A. F., Wang, H., Chellappan, M., Hammett, E., Yasuda, R., & Leong, K. W.
- Affiliations
- Howard Hughes Medical Institute (US)
- Duke University (US)
- Corresponding author
- Leong, Kam W.
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2014-07
- Volume
- 35
- Issue
- 20
- Pages
- 5327-5336
- ISSN
- 0142-9612 (ISSN-L)
- PMC
- PMC4023960
- OpenAlex
- W2086955856
- Cited by
- 102
- References
- 36
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 5 · 2023: 8 · 2022: 8 · 2021: 9 · 2020: 11 · 2019: 4 · 2018: 11 · 2017: 9 · 2016: 16 · 2015: 9 · 2014: 1
- FWCI
- 5.81
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Max Planck Digital Library (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- NIH (EB 015300)
- Howard Hughes Medical Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- substrate topography, direct reprogramming, fibroblast-to-neuron conversion, induced neurons, microposts, neurite outgrowth, dendritic branching, ASCL1, Brn2, MYT1L, VIP, CD90, BMP5, neuronal differentiation, cell-material interactions
- MeSH terms
- Animals, Biocompatible Materials, Cells, Cultured, Fibroblasts, Immunohistochemistry, Nerve Tissue Proteins, Neurons, Transcription Factors, Gene Expression, Neurites, Cell Culture Techniques, Regenerative Medicine, Mice, Neurogenesis, Cellular Reprogramming
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