Resetting Human Naïve Pluripotency

Jian-yun, Xiao; Daniel, H; Xie, Liangqi

doi:10.4137/geg.s38093

Cited by 6 publications

(7 citation statements)

References 28 publications

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“…Recently, significant effort has been made towards driving PSCs towards a so-called ‘naive’ ground state, which is believed to be the only true totipotent type of cell with no differentiation bias. However, so far many studies have only partially managed to recapitulate ground state requiring additional study [ 142 ].…”

Section: Sources Of Cells For Transplantationmentioning

confidence: 99%

Cellular regeneration strategies for macular degeneration: past, present and future

Chichagova

Hallam

Collin

et al. 2018

Eye

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Despite considerable effort and significant therapeutic advances, age-related macular degeneration (AMD) remains the commonest cause of blindness in the developed world. Progressive late-stage AMD with outer retinal degeneration currently has no proven treatment. There has been significant interest in the possibility that cellular treatments may slow or reverse visual loss in AMD. A number of modes of action have been suggested, including cell replacement and rescue, as well as immune modulation to delay the neurodegenerative process. Their appeal in this enigmatic disease relate to their generic, non-pathway-specific effects. The outer retina in particular has been at the forefront of developments in cellular regenerative therapies being surgically accessible, easily observable, as well as having a relatively simple architecture. Both the retinal pigment epithelium (RPE) and photoreceptors have been considered for replacement therapies as both sheets and cell suspensions. Studies using autologous RPE, and to a lesser extent, foetal retina, have shown proof of principle. A wide variety of cell sources have been proposed with pluripotent stem cell-derived cells currently holding the centre stage. Recent early-phase trials using these cells for RPE replacement have met safety endpoints and hinted at possible efficacy. Animal studies have confirmed the promise that photoreceptor replacement, even in a completely degenerated outer retina may restore some vision. Many challenges, however, remain, not least of which include avoiding immune rejection, ensuring long-term cellular survival and maximising effect. This review provides an overview of progress made, ongoing studies and challenges ahead.

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Section: Sources Of Cells For Transplantationmentioning

confidence: 99%

Cellular regeneration strategies for macular degeneration: past, present and future

Chichagova

Hallam

Collin

et al. 2018

Eye

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“…These cells reside in socalled naïve state. That state is quickly switched into a primed state of the postimplantation epiblasts via epigenetic modifications and changes in key pluripotency factors 64 . Naïve pluripotent stem cells have molecular and functional differences in comparison to primed state epiblast stem cells 64 .…”

Section: Generation Of Ipscsmentioning

confidence: 99%

“…That state is quickly switched into a primed state of the postimplantation epiblasts via epigenetic modifications and changes in key pluripotency factors 64 . Naïve pluripotent stem cells have molecular and functional differences in comparison to primed state epiblast stem cells 64 . Therefore, a screening approach is going on to identify reprogramming factors and/or small molecules, which would be efficient in stabilizing the naïve pluripotent state.…”

Section: Generation Of Ipscsmentioning

confidence: 99%

The potential of induced pluripotent stem cells as a tool to study skeletal dysplasias and cartilage-related pathologic conditions

Liu

Yang

et al. 2017

Osteoarthritis and Cartilage

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The development of induced pluripotent stem cells (iPSCs) technology has opened up new horizons for development of new research tools especially for skeletal dysplasias, which often lack human disease models. Regenerative medicine and tissue engineering could be the next areas to benefit from refinement of iPSC methods to repair focal cartilage defects, while applications for osteoarthritis (OA) and drug screening have evolved rather slowly. Although the advances in iPSC research of skeletal dysplasias and repair of focal cartilage lesions are not directly relevant to OA, they can be considered to pave the way to future prospects and solutions to OA research, too. The same problems which face the present cell-based treatments of cartilage injuries concern also the iPSC-based ones. However, established iPSC lines, which have no genomic aberrations and which efficiently differentiate into extracellular matrix secreting chondrocytes, could be an invaluable cell source for cell transplantations in the future. The safety issues concerning the recipient risks of teratoma formation and immune response still have to be solved before the potential use of iPSCs in cartilage repair of focal cartilage defects and OA.

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“…Naïve pluripotency affords certain advantages over traditionally derived primed ESCs, including improved proliferation and developmental potential as well as single-cell cloning efficiency and genome editing [11,12]. Consequently, a great deal of effort has been focused on both the reprogramming and establishment of naïve human ESC lines [9,13,14].…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic analysis of naïve human embryonic stem cells cultured in three-dimensional PEG scaffolds

McKee

Brown

Bakshi

et al. 2020

Preprint

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Derivation of primed and naïve human embryonic stem cells (ESCs) have prompted an increased interest in devising culture conditions for maintaining their pluripotency and differential potential. Naïve ESCs are characterized by improved viability, proliferation, and differentiation capacity in comparison to primed ESCs. However, traditional two-dimensional (2-D) cell culture techniques fail to mimic the three-dimensional (3-D) in vivo microenvironment, which results in altered morphological and molecular characteristics of ESCs. Here, we describe the use of 3-D self-assembling scaffolds that support growth and maintenance of the naïve state characteristics of human ESC line, Elf1. Scaffolds were formed via a Michael addition reaction upon combination of two 8-arm polyethylene glycol (PEG) polymers functionalized with thiol (PEG-8-SH) and acrylate (PEG-8-Acr) end groups. 3-D scaffolds not only maintained the naïve state, but also supported long-term growth for up to 3 weeks without requiring routine passaging and manipulation. 3-D grown cells exhibited upregulation of core (OCT4, NANOG, and SOX2) and naïve (KLF17, KLF4, TFCP2L1, DPPA3, and DNMT3L) genes. These genes returned to normal levels when 3-D grown cells were propagated under 2-D culture conditions. Examination of RNA-sequencing demonstrated significant changes in gene expression profiles between 2-D and 3-D grown Elf1 cells. Gene Ontology analysis revealed upregulation of biological processes involved in the regulation of transcription and translation, as well as β-catenin-TCF complex assembly, extracellular matrix organization, and chromatin remodeling in 3-D grown Elf1 cells. 3-D culture conditions also induced upregulation of genes associated with several signaling pathways including Wnt signaling and focal adhesion. However, p53 signaling pathway associated genes were downregulated under these culture conditions. Our findings provide insight into the possible mechanisms of prolonged self-renewal as well as upregulation of pluripotent genes stimulated by the transduction of mechanical signals from the 3-D microenvironment.

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Resetting Human Naïve Pluripotency

Cited by 6 publications

References 28 publications

Cellular regeneration strategies for macular degeneration: past, present and future

Cellular regeneration strategies for macular degeneration: past, present and future

The potential of induced pluripotent stem cells as a tool to study skeletal dysplasias and cartilage-related pathologic conditions

Transcriptomic analysis of naïve human embryonic stem cells cultured in three-dimensional PEG scaffolds

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