Nicotinamide promotes formation of retinal organoids from human pluripotent stem cells via enhanced neural cell fate commitment
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ABSTRACT:
PROVIDER: PRJNA692366 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13442846_1.fastq.gz | Fastqsanger.gz | |||
| SRR13442846_2.fastq.gz | Fastqsanger.gz | |||
| SRR13442847_1.fastq.gz | Fastqsanger.gz | |||
| SRR13442847_2.fastq.gz | Fastqsanger.gz | |||
| SRR13442848_1.fastq.gz | Fastqsanger.gz |
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Project description:Retinal organoids (ROs) derived from human pluripotent stem cells (hPSCs) recapitulate key features of human retinogenesis and thus provide a promising platform to study the mechanisms of retinal development and disease in a human context and to evaluate therapies. Although multiple differentiation protocols are currently in use, hPSCs exhibit tremendous variability in differentiation efficiency, with some cell lines consistently yielding few or even no ROs thus limiting their utility in research. To improve the efficiency and robustness of RO generation, we set out to identify factors that promote neural retina differentiation from hPSCs. We report here that nicotinamide (NAM) treatment at the early stage of differentiation significantly improved RO yield across 8 hPSC lines from different donors. Importantly, NAM treatment enabled efficient production of ROs from cell lines that would otherwise fail to generate meaningful number of ROs. Further analyses revealed that NAM treatment promotes neural commitment of hPSCs at the expense of non-neural ectodermal cell fate, which in turn increases eye field commitment and RO generation. This effect is mediated, at least in part, through inhibition of BMP signaling. Thus, our modified protocol with a simple NAM treatment improves the yield of ROs in all lines tested, and importantly greatly benefits to cell lines that previously proved to be intractable in retinal differentiation. Our data should facilitate the broader use of human ROs for disease modeling applications requiring the use of multiple cell lines or a larger scale of cell source such as therapy screening.
2022-06-14 | GSE164884 | GEO
Project description:Retinal organoids (ROs) derived from human pluripotent stem cells (hPSCs) recapitulate key features of retinogenesis and provide a promising platform to study retinal development and disease in a human context. Although multiple protocols are currently in use, hPSCs exhibit tremendous variability in differentiation efficiency, with some cell lines consistently yielding few or even no ROs, limiting their utility in research. We report here that early nicotinamide (NAM) treatment significantly improves RO yield across 8 hPSC lines from different donors, including some that would otherwise fail to generate a meaningful number of ROs. NAM treatment promotes neural commitment of hPSCs at the expense of non-neural ectodermal cell fate, which in turn increases eye field progenitor generation. Further analysis suggests that this effect is partially mediated through inhibition of BMP signaling. Our data encourage a broader use of human ROs for disease modeling applications that require the use of multiple patient-specific cell lines.
| S-EPMC9247291 | biostudies-literature
Project description:Culture of hematopoietic stem and progenitor cells in the presence of thrombopoietin induces megakaryocytic differentiation. Addition of nicotinamide to thrombopoietin-stimulated cultures results in significant increases in megkaryocytic differentiation including greater polyploidization and enhanced proplatelet formation. This study focuses on understanding the differences in the temporal gene expression pattern during differentiation with and without nicotinamide. Nicotinamide was added on day 5. Experiment Overall Design: Two biological experiments were analyzed. For each experiment, a sample was taken on day 5, before nicotinamide addition, and on days 6, 8, and 10 from both nicotinamide and control treated cultures. Each sample was analyzed in duplicate for a total of 14 hybridizations per culture or 28 total hybridizations.
2009-04-08 | E-GEOD-4974 | biostudies-arrayexpress
Project description:Culture of hematopoietic stem and progenitor cells in the presence of thrombopoietin induces megakaryocytic differentiation. Addition of nicotinamide to thrombopoietin-stimulated cultures results in significant increases in megkaryocytic differentiation including greater polyploidization and enhanced proplatelet formation. This study focuses on understanding the differences in the temporal gene expression pattern during differentiation with and without nicotinamide. Nicotinamide was added on day 5. Keywords: treatment response
2006-08-25 | GSE4974 | GEO
Project description:Nicotinamide (NAM) inhibited the expression of Age related macular degeneration (AMD) associated proteins in hiPSC-derived retinal pigment epithelium (RPE). We did the microarray analysis to examine the global impact of NAM on hiPSC-derived RPE transcriptome in order to better understand the mechanism of action of NAM.
2018-01-15 | GSE76923 | GEO
Project description:Retinal microvascularization can provide important informations to systemic vascular phenomena. The non-invasive quantitative description of the retinal vascularization is now possible by performing OCT-angiography and their image analysis software (vascular density and retinal perfusion). Systemic microvacular changes during the establishment of oncological treatment by targeted antiangiogenic therapy are little described in the literature. The objective of this pilot study is to describe the evolution of the retinal vascular density of patients with antiangiogenic drugs. In addition, the evolution of the retinal vascular density of patients on antiangiogenic drugs will study as a function of the response to the treatment and the toxicity of these treatments.
| 2382594 | ecrin-mdr-crc
Project description:Heart failure with preserved ejection fraction (HFpEF) is a highly prevalent and intractable form of cardiac decompensation commonly associated with diastolic dysfunction. Here, we show that diastolic dysfunction in patients with HFpEF is associated with a cardiac deficit in nicotinamide adenine dinucleotide (NAD+). Elevating NAD+ by oral supplementation of its precursor, nicotinamide, improved diastolic dysfunction induced by aging (in 2-year-old C57BL/6J mice), hypertension (in Dahl salt-sensitive rats) or cardiometabolic syndrome (in ZSF1 obese rats). Mechanistically, this effect was mediated partly through alleviated systemic comorbidities and enhanced myocardial bioenergetics, as evidenced by cardiac trasncriptome and metabolome analyses. Simultaneously, nicotinamide directly improved cardiomyocyte passive stiffness and calcium-dependent active relaxation through increased deacetylation of titin and the sarcoplasmic reticulum calcium ATPase 2a, respectively. In a long-term human cohort study, high dietary intake of naturally occurring NAD+ precursors was associated with lower blood pressure and reduced risk of cardiac mortality. Collectively, these results suggest NAD+ precursors, and especially nicotinamide, as potential therapeutic agents to treat diastolic dysfunction and HFpEF in humans.
2021-02-11 | GSE163665 | GEO
Project description:Nicotinamide, a main precursor of NAD+, is essential for cellular fuel respiration, energy production, and other cellular processes. Transporters for other precursors of NAD+ such as nicotinic acid and nicotinamide mononucleotide have been identified, but the cellular transporter of nicotinamide has not been elucidated. Here, we demonstrated that equilibrative nucleoside transporters 1 and 2 (ENT1 and 2, encoded by SLC29A1/2) drove cellular nicotinamide uptake and set nicotinamide metabolism homeostasis. In addition, ENT1/2 exhibited a strong capacity to change the composition of cellular metabolites and the profile of transcripts, especially those related to nicotinamide. Then, we further found that ENT1/2 could regulate cellular respiration and senescence, which are universally acknowledged as nicotinamide biological functions, to which the NAD+ pool level and mitochondrial status influenced by ENT1/2 made important contributions. Together, ENT1 and ENT2 act as both cellular nicotinamide-level keepers and nicotinamide biological regulators through their NAM transport functions.
2025-01-01 | GSE251776 | GEO
Project description:Age-related macular degeneration (AMD), featured with dysfunction and loss of retinal pigment epithelium (RPE), is lacking efficient therapeutic approaches. According to our previous studies, human amniotic epithelial stem cells (hAESCs) may serve as a potential seed cell source of RPE cells for therapy because they have no ethical concerns, no tumorigenicity, and little immunogenicity. Herein, trichostatin A and nicotinamide can direct hAESCs differentiation into RPE like cells. The differentiated cells display the morphology, marker expression and cellular function of the native RPE cells, and noticeably express little MHC class II antigens and high level of HLA-G. Importantly, visual function and retinal structure of Royal College of Surgeon (RCS) rats, a classical animal model of retinal degeneration, were rescued after subretinal transplantation with the hAESCs-derived RPE like cells. We established a high-efficient, low-cost and safety-guaranteed system for generating functional RPE cells from hAESCs. These results suggest a novel and ideal therapeutic strategy for retinal degeneration diseases
2021-10-20 | GSE180616 | GEO
Project description:To investigate the efficacy of nicotinamide treatment using our ex-vivo primary lymphocyte model, we performed high-throughput RNA sequencing on libraries generated from untreated and nicotinamide treated samples. PBMC isolated from FRDA affected individuals were cultured to prepare the primary lymphocyte cell lines. The primary cultured cells were either treated with 10mM nicotinamide or without the addition of drug during the 3-days treatment. RNA was extracted after the treatment and then RNA-seq libraries were generated by standard protocols.
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