scholarly journals Transcriptome Dynamics of Human Neuronal Differentiation From iPSC

2021 ◽  
Vol 9 ◽  
Author(s):  
Meltem Kuruş ◽  
Soheil Akbari ◽  
Doğa Eskier ◽  
Ahmet Bursalı ◽  
Kemal Ergin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neuronal Differentiation ◽  
De Novo ◽  
Neurological Diseases ◽  
Transcriptome Assembly ◽  
Embryonic Stem ◽  
Protein Coding ◽  
Regulatory Factors ◽  
Adult Cell ◽  
Induced Pluripotent

The generation and use of induced pluripotent stem cells (iPSCs) in order to obtain all differentiated adult cell morphologies without requiring embryonic stem cells is one of the most important discoveries in molecular biology. Among the uses of iPSCs is the generation of neuron cells and organoids to study the biological cues underlying neuronal and brain development, in addition to neurological diseases. These iPSC-derived neuronal differentiation models allow us to examine the gene regulatory factors involved in such processes. Among these regulatory factors are long non-coding RNAs (lncRNAs), genes that are transcribed from the genome and have key biological functions in establishing phenotypes, but are frequently not included in studies focusing on protein coding genes. Here, we provide a comprehensive analysis and overview of the coding and non-coding transcriptome during multiple stages of the iPSC-derived neuronal differentiation process using RNA-seq. We identify previously unannotated lncRNAs via genome-guided de novo transcriptome assembly, and the distinct characteristics of the transcriptome during each stage, including differentially expressed and stage specific genes. We further identify key genes of the human neuronal differentiation network, representing novel candidates likely to have critical roles in neurogenesis using coexpression network analysis. Our findings provide a valuable resource for future studies on neuronal differentiation.

scholarly journals Reprogramming triggers endogenous L1 and Alu retrotransposition in human induced pluripotent stem cells

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Sabine Klawitter ◽  
Nina V. Fuchs ◽  
Kyle R. Upton ◽  
Martin Muñoz-Lopez ◽  
Ruchi Shukla ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
De Novo ◽  
Embryonic Stem ◽  
Protein Coding ◽  
Induced Pluripotent ◽  
Hesc Lines

Abstract Human induced pluripotent stem cells (hiPSCs) are capable of unlimited proliferation and can differentiate in vitro to generate derivatives of the three primary germ layers. Genetic and epigenetic abnormalities have been reported by Wissing and colleagues to occur during hiPSC derivation, including mobilization of engineered LINE-1 (L1) retrotransposons. However, incidence and functional impact of endogenous retrotransposition in hiPSCs are yet to be established. Here we apply retrotransposon capture sequencing to eight hiPSC lines and three human embryonic stem cell (hESC) lines, revealing endogenous L1, Alu and SINE-VNTR-Alu (SVA) mobilization during reprogramming and pluripotent stem cell cultivation. Surprisingly, 4/7 de novo L1 insertions are full length and 6/11 retrotransposition events occurred in protein-coding genes expressed in pluripotent stem cells. We further demonstrate that an intronic L1 insertion in the CADPS2 gene is acquired during hiPSC cultivation and disrupts CADPS2 expression. These experiments elucidate endogenous retrotransposition, and its potential consequences, in hiPSCs and hESCs.

scholarly journals Identification of Molecular Signatures in Neural Differentiation and Neurological Diseases Using Digital Color-Coded Molecular Barcoding

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Debora Salerno ◽  
Alessandro Rosa
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Neural Differentiation ◽  
Disease Modeling ◽  
Neurological Diseases ◽  
Embryonic Stem ◽  
Molecular Signatures ◽  
Molecular Barcoding ◽  
Induced Pluripotent

Human pluripotent stem cells (PSCs), including embryonic stem cells and induced pluripotent stem cells, represent powerful tools for disease modeling and for therapeutic applications. PSCs are particularly useful for the study of development and diseases of the nervous system. However, generating in vitro models that recapitulate the architecture and the full variety of subtypes of cells that make the complexity of our brain remains a challenge. In order to fully exploit the potential of PSCs, advanced methods that facilitate the identification of molecular signatures in neural differentiation and neurological diseases are highly demanded. Here, we review the literature on the development and application of digital color-coded molecular barcoding as a potential tool for standardizing PSC research and applications in neuroscience. We will also describe relevant examples of the use of this technique for the characterization of the heterogeneous composition of the brain tumor glioblastoma multiforme.

scholarly journals Transcriptional programs regulating neuronal differentiation are disrupted in DLG2 knockout human embryonic stem cells and enriched for schizophrenia and related disorders risk variants

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Bret Sanders ◽  
Daniel D’Andrea ◽  
Mark O. Collins ◽  
Elliott Rees ◽  
Tom G. J. Steward ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Neuronal Differentiation ◽  
Human Embryonic Stem Cells ◽  
De Novo ◽  
Embryonic Stem ◽  
Neuropsychiatric Disorders ◽  
Loss Of Function ◽  
Excitatory Neurons

AbstractCoordinated programs of gene expression drive brain development. It is unclear which transcriptional programs, in which cell-types, are affected in neuropsychiatric disorders such as schizophrenia. Here we integrate human genetics with transcriptomic data from differentiation of human embryonic stem cells into cortical excitatory neurons. We identify transcriptional programs expressed during early neurogenesis in vitro and in human foetal cortex that are down-regulated in DLG2−/− lines. Down-regulation impacted neuronal differentiation and maturation, impairing migration, morphology and action potential generation. Genetic variation in these programs is associated with neuropsychiatric disorders and cognitive function, with associated variants predominantly concentrated in loss-of-function intolerant genes. Neurogenic programs also overlap schizophrenia GWAS enrichment previously identified in mature excitatory neurons, suggesting that pathways active during prenatal cortical development may also be associated with mature neuronal dysfunction. Our data from human embryonic stem cells, when combined with analysis of available foetal cortical gene expression data, de novo rare variants and GWAS statistics for neuropsychiatric disorders and cognition, reveal a convergence on transcriptional programs regulating excitatory cortical neurogenesis.

Reversine: A Synthetic Purine with a Dual Activity as a Cell Dedifferentiating Agent and a Selective Anticancer Drug

2020 ◽  
Vol 27 (21) ◽  
pp. 3448-3462
Author(s):  
Marco Piccoli ◽  
Andrea Ghiroldi ◽  
Michelle M. Monasky ◽  
Federica Cirillo ◽  
Giuseppe Ciconte ◽  
...  
Keyword(s):  
Stem Cells ◽  
Current Knowledge ◽  
Embryonic Stem ◽  
Cell Types ◽  
Cancer Drug ◽  
Anti Cancer ◽  
Adult Cell ◽  
Induced Pluripotent

The development of new therapeutic applications for adult and embryonic stem cells has dominated regenerative medicine and tissue engineering for several decades. However, since 2006, induced Pluripotent Stem Cells (iPSCs) have taken center stage in the field, as they promised to overcome several limitations of the other stem cell types. Nonetheless, other promising approaches for adult cell reprogramming have been attempted over the years, even before the generation of iPSCs. In particular, two years before the discovery of iPSCs, the possibility of synthesizing libraries of large organic compounds, as well as the development of high-throughput screenings to quickly test their biological activity, enabled the identification of a 2,6-disubstituted purine, named reversine, which was shown to be able to reprogram adult cells to a progenitor-like state. Since its discovery, the effect of reversine has been confirmed on different cell types, and several studies on its mechanism of action have revealed its central role in inhibitory activity on several kinases implicated in cell cycle regulation and cytokinesis. These key features, together with its chemical nature, suggested a possible use of the molecule as an anti-cancer drug. Remarkably, reversine exhibited potent cytotoxic activity against several tumor cell lines in vitro and a significant effect in decreasing tumor progression and metastatization in vivo. Thus, 15 years since its discovery, this review aims at critically summarizing the current knowledge to clarify the dual role of reversine as a dedifferentiating agent and anti-cancer drug.

scholarly journals Quantitative glycomics monitoring of induced pluripotent- and embryonic stem cells during neuronal differentiation

2014 ◽  
Vol 13 (3) ◽  
pp. 454-464 ◽  
Author(s):  
Michiyo Terashima ◽  
Maho Amano ◽  
Tomohiro Onodera ◽  
Shin-Ichiro Nishimura ◽  
Norimasa Iwasaki
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Neuronal Differentiation ◽  
Embryonic Stem ◽  
Induced Pluripotent

Nuclear reprogramming and induced pluripotency

2019 ◽  
pp. 205-212
Author(s):  
John C. Lucchesi
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Late Onset ◽  
Neurological Diseases ◽  
Embryonic Stem ◽  
Induced Pluripotency ◽  
Differentiated Cells ◽  
Induced Pluripotent ◽  
Bivalent Promoter

Four core transcription factors known to maintain the pluripotent state in embryonic stem cells (ESCs)—Oct4, Sox2, Klf4 and c-Myc—were used to induce pluripotent stem cells in adult-derived fibroblasts. Induced pluripotent stem cells (iPSCs), like ESCs, have less condensed and more transcriptionally active chromatin than differentiated cells. The number of genes with bivalent promoter marks increases during reprogramming, reflecting the switch of differentiation-specific active genes to an inactive, but poised, status. The levels of DNA methyl transferases and demethylases are increased, underlying the changes in the pattern of DNA methylation that occur late during reprogramming. The potential therapeutic applications of iPSCs include reprogramming a patient’s own cells to avoid the problem of rejection following injection to restore tissue or organ function. iPSCs derived from individuals at risk of developing late-onset neurological diseases could be differentiated in culture to predict the future occurrence of the disease. Caveats involve the fact that long-term culturing often results in genomic mutations that may, by chance, involve tumor suppressors or oncogenes.

scholarly journals Integrative Research of Induction of Pluripotent Stem Cells

2017 ◽  
Vol 4 (3-4) ◽  
pp. 115-124 ◽  
Author(s):  
Penglin Gao ◽  
Chuanhe Sun ◽  
Weilong Liao ◽  
Wenfei Jiang ◽  
Te Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Viral Vector ◽  
Neurological Diseases ◽  
Embryonic Stem ◽  
Basic Research ◽  
Model Systems ◽  
Suitable Model ◽  
Integrative Research ◽  
Induced Pluripotent

Since the Japanese scientist Shinya Yamanaka used a viral vector to transfer the combination of 4 factors into differentiated somatic cells and reprogramed them to obtain similar embryonic stem cells and induced pluripotent stem cells (iPSCs), it provided one integrative method for studying many medical fields. Patient-derived iPSCs have provided an opportunity to study human diseases for which no suitable model systems are available. iPSC technology has since become a major breakthrough in the field of stem cell research. With the continuous development of iPSC technology and the continuous improvement of technical levels, excellent advances have become more and more common in the basic research and medical fields of life sciences. This article reviews the development history, clinical application, and problems and prospects of iPSC, and focuses on the application of iPSC in neurological diseases.

scholarly journals Current Bioengineering Methods for Whole Kidney Regeneration

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Shuichiro Yamanaka ◽  
Takashi Yokoo
Keyword(s):  
Stem Cells ◽  
Kidney Disease ◽  
De Novo ◽  
Embryonic Stem ◽  
Kidney Regeneration ◽  
Innovative Strategies ◽  
Kidney Dialysis ◽  
Induced Pluripotent ◽  
End Stage ◽  
Embryonic Organ

Kidney regeneration is likely to provide an inexhaustible source of tissues and organs for immunosuppression-free transplantation. It is currently garnering considerable attention and might replace kidney dialysis as the ultimate therapeutic strategy for renal failure. However, anatomical complications make kidney regeneration difficult. Here, we review recent advances in the field of kidney regeneration, including (i) the directed differentiation of induced pluripotent stem cells/embryonic stem cells into kidney cells; (ii) blastocyst decomplementation; (iii) use of a decellularized cadaveric scaffold; (iv) embryonic organ transplantation; and (v) use of a nephrogenic niche for growing xenoembryos forde novokidney regeneration from stem cells. All these approaches represent potentially promising therapeutic strategies for the treatment of patients with chronic kidney disease. Although many obstacles to kidney regeneration remain, we hope that innovative strategies and reliable research will ultimately allow the restoration of renal function in patients with end-stage kidney disease.

Mini Review; Differentiation of Human Pluripotent Stem Cells into Oocytes

2020 ◽  
Vol 15 (4) ◽  
pp. 301-307 ◽  
Author(s):  
Gaifang Wang ◽  
Maryam Farzaneh
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Human Pluripotent Stem Cells ◽  
Human Oocyte ◽  
Differentiation Potential ◽  
Cell Lineages ◽  
Cell Based Therapy ◽  
Induced Pluripotent

Primary Ovarian Insufficiency (POI) is one of the main diseases causing female infertility that occurs in about 1% of women between 30-40 years of age. There are few effective methods for the treatment of women with POI. In the past few years, stem cell-based therapy as one of the most highly investigated new therapies has emerged as a promising strategy for the treatment of POI. Human pluripotent stem cells (hPSCs) can self-renew indefinitely and differentiate into any type of cell. Human Embryonic Stem Cells (hESCs) as a type of pluripotent stem cells are the most powerful candidate for the treatment of POI. Human-induced Pluripotent Stem Cells (hiPSCs) are derived from adult somatic cells by the treatment with exogenous defined factors to create an embryonic-like pluripotent state. Both hiPSCs and hESCs can proliferate and give rise to ectodermal, mesodermal, endodermal, and germ cell lineages. After ovarian stimulation, the number of available oocytes is limited and the yield of total oocytes with high quality is low. Therefore, a robust and reproducible in-vitro culture system that supports the differentiation of human oocytes from PSCs is necessary. Very few studies have focused on the derivation of oocyte-like cells from hiPSCs and the details of hPSCs differentiation into oocytes have not been fully investigated. Therefore, in this review, we focus on the differentiation potential of hPSCs into human oocyte-like cells.

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