Mechanisms of cellular rejuvenation

Denoth-Lippuner, Annina; Jessberger, Sebastian

doi:10.1002/1873-3468.13483

Cited by 8 publications

(9 citation statements)

References 73 publications

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“…While full rejuvenation to a pluripotent state resets the epigenetic signatures of the cellular source almost completely [46,47] (and reviewed in this issue [16]), little is known about epigenetic memory in iNSCs. While full rejuvenation to a pluripotent state resets the epigenetic signatures of the cellular source almost completely [46,47] (and reviewed in this issue [16]), little is known about epigenetic memory in iNSCs.…”

Section: Molecular Mechanisms Regulating Direct Conversion Of Somaticmentioning

confidence: 99%

“…Apart from potential pluripotency intermediates, transdifferentiated cells might harbor somatic memory. While full rejuvenation to a pluripotent state resets the epigenetic signatures of the cellular source almost completely [46,47] (and reviewed in this issue [16]), little is known about epigenetic memory in iNSCs. Interestingly, Thier et al [28] reported the expression of fibroblast marker COL3A1 in fibroblast-derived, but not blood-derived iNSCs.…”

Section: Molecular Mechanisms Regulating Direct Conversion Of Somaticmentioning

confidence: 99%

“…Instead, iPSCs display an almost complete epigenetic reset, whereas iNs maintain most of the epigenetic marks, a phenomenon that is comprehensively addressed by Denoth-Lippuner and Jessberger in this issue [16]. Hence, we review the cutting-edge nonintegrating methods for the delivery of TFs and comprehensively discuss the distinct outcomes of different iNSC conversion protocols in terms of cellular markers, differentiation potential, and physiological functions of the neural progeny.…”

mentioning

confidence: 99%

“…Moreover, epigenetic marks that are present in the somatic cell population, including those correlating with aging, are differently erased by the reprogramming pathways. Instead, iPSCs display an almost complete epigenetic reset, whereas iNs maintain most of the epigenetic marks, a phenomenon that is comprehensively addressed by Denoth-Lippuner and Jessberger in this issue [16]. iNSCs can be produced faster and more cost-efficient than iPSC-derived NSCs, and also harbor less tumor formation potential.…”

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confidence: 99%

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Take the shortcut – direct conversion of somatic cells into induced neural stem cells and their biomedical applications

et al. 2019

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Second-generation reprogramming of somatic cells directly into the cell type of interest avoids induction of pluripotency and subsequent cumbersome differentiation procedures. Several recent studies have reported direct conversion of human somatic cells into stably proliferating induced neural stem cells (iNSCs). Importantly, iNSCs are easier, faster, and more cost-efficient to generate than induced pluripotent stem cells (iPSCs), and also have a higher level of clinical safety. Stably, self-renewing iNSCs can be derived from different cellular sources, such as skin fibroblasts and peripheral blood mononuclear cells, and readily differentiate into neuronal and glial lineages that are indistinguishable from their iPSC-derived counterparts or from NSCs isolated from primary tissues. This review focuses on the derivation and characterization of iNSCs and their biomedical applications. We first outline different approaches to generate iNSCs and then discuss the underlying molecular mechanisms. Finally, we summarize the preclinical validation of iNSCs to highlight that these cells are promising targets for disease modeling, autologous cell therapy, and precision medicine. Take the shortcut: from iPSC to iNSCForced expression of lineage-specific transcription factors (TFs) has been shown to reprogram the developmental potential of various somatic cell types e.g. by inducing pluripotency [1]. The seminal breakthrough of fibroblast reprogramming into iPSCs offers a novel experimental tool to generate patient-specific cells for developmental studies and diverse biomedical applications, such as disease modeling and cell therapy. Since then, efficiency and robustness of reprogramming protocols have been substantially improved, but the derivation of patient-specific iPSCs remains a lengthy and cumbersome procedure. Moreover, clinical applications require subsequent redifferentiation of iPSCs into the cell type of interest, which is inefficient and risky because transplanted undifferentiated iPSCs are tumorigenic. In the shadow of iPSC-type reprogramming, second-generation reprogramming paradigms have been developed to bypass the pluripotency state Abbreviations

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Section: Molecular Mechanisms Regulating Direct Conversion Of Somaticmentioning

confidence: 99%

Section: Molecular Mechanisms Regulating Direct Conversion Of Somaticmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Take the shortcut – direct conversion of somatic cells into induced neural stem cells and their biomedical applications

et al. 2019

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“…In this Special Issue of FEBS Letters entitled 'Neural and Hematopoietic Stem Cell Reprogramming', we present a collection of peer-reviewed original articles and reviews authored by select international experts. They discuss the most exciting recent developments in the field, focusing on hematopoietic [1][2][3][4][5] and neural [6][7][8][9][10] (stem) cell generation/reprogramming in vitro. The future research directions and the obstacles ahead are also put into perspective.…”

mentioning

confidence: 99%