Generation of diverse neural cell types through direct conversion

Petersen, Gayle F; Strappe, Pádraig

doi:10.4252/wjsc.v8.i2.32

Cited by 10 publications

(8 citation statements)

References 158 publications

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“…Transcription factors NFIa, NFIb and Ptbp1 indicated an astrocytic cell type. 11 , 34 - 36 The NFI family played important roles in the development of the central nervous system. 37 , 38 The study by Deneen et al indicated that NFIa was important in the transition from neurogenesis to gliogenesis.…”

Section: Discussionmentioning

confidence: 99%

Reprogramming of mouse fibroblasts into neural lineage cells using biomaterials

Kantawong¹,

Saksiriwisitkul²,

Riyapa³

et al. 2018

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Introduction: Induced neural stem cells (iNSCs) have the ability of differentiation into neurons, astrocytes and oligodendrocytes. iNSCs are very useful in terms of research and treatment. The present study offers an idea that biomaterials could be one of the tools that could modulate reprogramming process in the fibroblasts. Methods: Gelatin biomaterials were fabricated into 3 types, including (i) gelatin, (ii) gelatin with 1 mg/mL hydroxyapatite, and (iii) gelatin with hydroxyapatite and pig brain. NIH/3T3 fibroblasts were cultured on each type of biomaterial for 7, 9 and 14 days. RT-PCR was performed to investigate the gene expression of the fibroblasts on biomaterials compared to the fibroblasts on tissue culture plates. PI3K/Akt signaling was performed by flow cytometry after 24 hours seeding on the biomaterials. The biomaterials were also tested with the human APCs and PDL cells. Results: The fibroblasts exhibited changes in the expression of the reprogramming factor; Klf‫4 and the neural transcription factors; NFIa, NFIb and Ptbp1 after 9 days culture. The cultivation of fibroblasts on the biomaterials for 7 days showed a higher expression of the transcription factor SOX9. The expression of epigenetic genes; Kat2a and HDAC3 were changed upon the cultivation on the biomaterials for 9 days. The fibroblasts cultured on the biomaterials showed an activation of PI3K/Akt signaling. The human APCs and human PDL cells developed mineralization process on biomaterials Conclusion: Changes in the expression of Klf4, NFIa, NFIb, Ptbp1 and SOX9 indicated that fibroblasts were differentiated into an astrocytic lineage. It is possible that the well-designed biomaterials could work as powerful tools in the reprogramming process of fibroblasts into iNSCs.

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Section: Discussionmentioning

confidence: 99%

Reprogramming of mouse fibroblasts into neural lineage cells using biomaterials

Kantawong¹,

Saksiriwisitkul²,

Riyapa³

et al. 2018

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“…As in the pancreas and heart, iPSCs, embryonic stem cells (ESCs), and adult stem cells (i.e., mesenchymal stem cells) can differentiate into neurons in vitro ; however, the drawbacks of stem cell–based therapy include its potential tumorigenicity, the difficulty of generating diverse neuronal cell types, and the lack of full functionality in the induced neurons (Huang et al, 2015; Petersen et al, 2016). The direct conversion of glia/astrocytes to neuron-like cells in situ offers an alternative and promising strategy.…”

Section: Regeneration In Non-mammalian Vertebrates and Other Mammamentioning

confidence: 99%

“…By using pharmacologic and genetic methods, investigators determined that zinc-dependent HDACs are required for liver regeneration (Huang et al, 2013) and that overexpressing SIRT1 (a Class III HDAC) also suppressed hepatocyte proliferation by impairing farnesoid X receptor activity (Garcia-Rodriguez et al, 2014). Similarly, it has been thoroughly reviewed that epigenetic factors regulate the development and regeneration of pancreas (Avrahami et al, 2012; Migliorini et al, 2014), heart (Quaife-Ryan et al, 2016), and CNS (Arlotta et al, 2014; Petersen et al, 2016). …”

Section: Differences Between Hc Regeneration and Hc Developmentmentioning

confidence: 99%

Cochlear hair cell regeneration after noise-induced hearing loss: Does regeneration follow development?

Zheng

Zuo

2017

Hearing Research

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Noise-induced hearing loss (NIHL) affects a large number of military personnel and civilians. Regenerating inner-ear cochlear hair cells (HCs) is a promising strategy to restore hearing after NIHL. In this review, we first summarize recent transcriptome profile analysis of zebrafish lateral lines and chick utricles where spontaneous HC regeneration occurs after HC damage. We then discuss recent studies in other mammalian regenerative systems such as pancreas, heart and central nervous system. Both spontaneous and forced HC regeneration occurs in mammalian cochleae in vivo involving proliferation and direct lineage conversion. However, both processes are inefficient and incomplete, and decline with age. For direct lineage conversion in vivo in cochleae and in other systems, further improvement requires multiple factors, including transcription, epigenetic and trophic factors, with appropriate stoichiometry in appropriate architectural niche. Increasing evidence from other systems indicates that the molecular paths of direct lineage conversion may be different from those of normal developmental lineages. We therefore hypothesize that HC regeneration does not have to follow HC development and that epigenetic memory of supporting cells influences the HC regeneration, which may be a key to successful cochlear HC regeneration. Finally, we discuss recent efforts in viral gene therapy and drug discovery for HC regeneration. We hope that combination therapy targeting multiple factors and epigenetic signaling pathways will provide promising avenues for HC regeneration in humans with NIHL and other types of hearing loss.

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“…der Schizophrenie und bipolaren Störung von Bedeutung sein könnten. Hinzu kommt, dass die Zahl an neuronalen Zellen durch die geringe verfügbare Menge an Patientenmaterial als auch durch die post-mitotische Natur von Neuronen beschränkt ist (58).…”

Section: Original Articleunclassified

Anwendungen pluripotenter Stammzellen in der psychiatrischen Forschung

Rupp¹,

Papiol²,

Falkai³

et al. 2016

Die Psychiatrie

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Zusammenfassung Ausgangslage: Die Entwicklung von Technologien zur Herstellung sogenannter induzierter pluripotenter Stammzellen (iPSCs) und prinzipiell jeden Zelltyps von Patienten und gesunden Personen ermöglicht eine Vielzahl bislang nicht vorstellbarer Forschungsansätze im Bereich psychiatrischer Erkrankungen. Es können jetzt aussagekräftige zelluläre Systeme auch für genetisch komplexe Erkrankungen entwickelt werden, die auf Ebene des einzelnen Patienten und unter Erhalt der individuellen genetischen Information Analysen mit dramatisch erhöhter sogenannter „construct validity“ erlauben. Sowohl die genetische als auch die phänotypische Komplexität lässt allerdings vermuten, dass die meisten psychiatrischen Erkrankungen eher als syndromische Gruppen denn als definierte Einzelerkrankungen anzusehen sind. Deshalb ist es vermutlich von entscheidender Bedeutung, Patienten vor der Auswahl zur Reprogrammierung, durch genetische, molekulare und/oder phänotypische Profile, in repräsentative Subgruppen zu unterteilen. Diese Vorauswahl ist wegen der zu Grunde liegenden komplexen biologischen Veränderungen, aber insbesondere auch wegen des hohen experimentellen Aufwands, bei der Etablierung und Charakterisierung patienten-abgeleiteter Zellsysteme wichtig. Ausblick: Wir nehmen an, dass der Fokus auf subgruppen-repräsentative Zellsysteme entscheidend dazu beitragen wird, die prädiktive Aussagekraft dieses innovativen Forschungsansatzes im Bereich psychiatrischer Erkrankungen zu erhöhen.

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Generation of diverse neural cell types through direct conversion

Abstract: A characteristic of neurological disorders is the loss of critical populations of cells that the body is unable to replace, thus there has been much interest in identifying

Cited by 10 publications

References 158 publications

Reprogramming of mouse fibroblasts into neural lineage cells using biomaterials

Reprogramming of mouse fibroblasts into neural lineage cells using biomaterials

Cochlear hair cell regeneration after noise-induced hearing loss: Does regeneration follow development?

Anwendungen pluripotenter Stammzellen in der psychiatrischen Forschung

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