Magnetic Control of Axon Navigation in Reprogrammed Neurons

Jin, Yoonhee; Lee, Jung Uk; Chung, Eunna; Yang, Kisuk; Kim, Jin; Kim, Ji Wook; Lee, Jong Seung; Cho, Ann Na; Oh, Taekyu; Lee, Jae Hyun; Cho, Seung Woo; Cheon, Jinwoo

doi:10.1021/acs.nanolett.9b02756

Cited by 25 publications

(24 citation statements)

References 35 publications

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“…Such engineered MNPs have been used to modulate the spatial distribution of signaling molecules involved in cellular polarity, thus enabling the local formation of membrane protrusions [ 11 ]. Recent studies have proposed promising strategies with MNPs designed to activate specifically axonal growth in reprogrammed neurons from induced pluripotent stems cells [ 12 , 13 ]. However, these innovative approaches are very complex and will need further investigations before being really effective for therapeutic applications.…”

Section: Introductionmentioning

confidence: 99%

Parallelized Manipulation of Adherent Living Cells by Magnetic Nanoparticles-Mediated Forces

Bongaerts

Aïzel

Secret

et al. 2020

IJMS

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The remote actuation of cellular processes such as migration or neuronal outgrowth is a challenge for future therapeutic applications in regenerative medicine. Among the different methods that have been proposed, the use of magnetic nanoparticles appears to be promising, since magnetic fields can act at a distance without interactions with the surrounding biological system. To control biological processes at a subcellular spatial resolution, magnetic nanoparticles can be used either to induce biochemical reactions locally or to apply forces on different elements of the cell. Here, we show that cell migration and neurite outgrowth can be directed by the forces produced by a switchable parallelized array of micro-magnetic pillars, following the passive uptake of nanoparticles. Using live cell imaging, we first demonstrate that adherent cell migration can be biased toward magnetic pillars and that cells can be reversibly trapped onto these pillars. Second, using differentiated neuronal cells we were able to induce events of neurite outgrowth in the direction of the pillars without impending cell viability. Our results show that the range of forces applied needs to be adapted precisely to the cellular process under consideration. We propose that cellular actuation is the result of the force on the plasma membrane caused by magnetically filled endo-compartments, which exert a pulling force on the cell periphery.

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Section: Introductionmentioning

confidence: 99%

Parallelized Manipulation of Adherent Living Cells by Magnetic Nanoparticles-Mediated Forces

Bongaerts

Aïzel

Secret

et al. 2020

IJMS

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show abstract

“…Such engineered MNPs have been used to modulate the spatial distribution of signaling molecules involved in cellular polarity, thus enabling the local formation of membrane protrusions (Etoc et al 2015). Recent studies have proposed promising strategies with MNPs designed to activate specifically axonal growth in reprogrammed neurons from induced pluripotent stems cells (Jin et al 2019;Schöneborn et al 2019). However, these innovative approaches are very complex and will need further investigations before being really effective for therapeutic applications.…”

Section: Introductionmentioning

confidence: 99%

Parallelized manipulation of adherent living cells by magnetic nanoparticles-mediated forces

Bongaerts

Aïzel

Secret

et al. 2020

Preprint

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The remote actuation of cellular processes such as migration or neuronal outgrowth is a challenge for future therapeutic applications in regenerative medicine. Among the different methods that have been proposed, the use of magnetic nanoparticles appears to be promising since magnetic fields can act at a distance without interactions with the surrounding biological system. To control biological processes at a subcellular spatial resolution, magnetic nanoparticles can be used either to induce biochemical reactions locally or to apply forces on different elements of the cell. Here, we show that cell migration and neurite outgrowth can be directed by the forces produced by a switchable parallelized array of micro-magnetic pillars, following passive uptake of nanoparticles. Using live cell imaging, we first demonstrate that adherent cell migration can be biased toward magnetic pillars and that cells can be reversibly trapped onto these pillars. Second, using differentiated neuronal cells we were able to induce events of neurite outgrowth in the direction of the pillars without impending cell viability. Our results show that the range of forces applied needs to be adapted precisely to the cellular process under consideration. We propose that cellular actuation is the result of the force on the plasma membrane caused by magnetically filled endo-compartments, which exert a pulling force on the cell periphery.

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“…Before generating chromatin interaction data in NPC differentiation, we inspected our differentiation system from iPSC to NPC by confirming specific markers of each cell type. In previous studies, we already constructed iPSC maintenance and differentiation technique [ 23 , 24 , 34 ]. We re-confirmed the pluripotency of iPSCs using markers OCT4, E-cadherin (E-cad) and Tra-1-60 and verified NPC status through the elevated expression of Pax6, Sox2 and Nestin, with Ki67 as a cell-proliferation marker in NPC ( Figure 1 A).…”

Section: Resultsmentioning

confidence: 99%

“…Then we attached EBs in the new culture dish coated with Matrigel (BD Biosciences) with neural induction medium comprised of DMEM/F12 medium (11320033, Invitrogen), 1× N2 supplement (17502048, Invitrogen), 1× nonessential amino acids (11140050, Invitrogen) for 6 days. When neural rosette formation appeared in the center of the EBs, NPCs were collected for analysis [ 23 , 24 , 25 ].…”

Section: Methodsmentioning

confidence: 99%

Chromatin Interaction Changes during the iPSC-NPC Model to Facilitate the Study of Biologically Significant Genes Involved in Differentiation

Choi

Hwang

Lee

et al. 2020

Genes

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Given the difficulties of obtaining diseased cells, differentiation of neurons from patient-specific human induced pluripotent stem cells (iPSCs) with neural progenitor cells (NPCs) as intermediate precursors is of great interest. While cellular and transcriptomic changes during the differentiation process have been tracked, little attention has been given to examining spatial re-organization, which has been revealed to control gene regulation in various cells. To address the regulatory mechanism by 3D chromatin structure during neuronal differentiation, we examined the changes that take place during differentiation process using two cell types that are highly valued in the study of neurodegenerative disease - iPSCs and NPCs. In our study, we used Hi-C, a derivative of chromosome conformation capture that enables unbiased, genome-wide analysis of interaction frequencies in chromatin. We showed that while topologically associated domains remained mostly the same during differentiation, the presence of differential interacting regions in both cell types suggested that spatial organization affects gene regulation of both pluripotency maintenance and neuroectodermal differentiation. Moreover, closer analysis of promoter–promoter pairs suggested that cell fate specification is under the control of cis-regulatory elements. Our results are thus a resourceful addition in benchmarking differentiation protocols and also provide a greater appreciation of NPCs, the common precursors from which required neurons for applications in neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease, schizophrenia and spinal cord injuries are utilized.

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Magnetic Control of Axon Navigation in Reprogrammed Neurons

Cited by 25 publications

References 35 publications

Parallelized Manipulation of Adherent Living Cells by Magnetic Nanoparticles-Mediated Forces

Parallelized Manipulation of Adherent Living Cells by Magnetic Nanoparticles-Mediated Forces

Parallelized manipulation of adherent living cells by magnetic nanoparticles-mediated forces

Chromatin Interaction Changes during the iPSC-NPC Model to Facilitate the Study of Biologically Significant Genes Involved in Differentiation

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