Nicotinamide Promotes Cell Survival and Differentiation as Kinase Inhibitor in Human Pluripotent Stem Cells

Yang, Meng; Ren, Zhili; Xu, Faxiang; Zhou, Xiaoxiao; Song, Chengcheng; Wang, Vivien Ya-Fan; Liu, Weiwei; Lu, Ligong; Thomson, James A.; Chen, Guokai

doi:10.1016/j.stemcr.2018.10.023

Cited by 75 publications

(71 citation statements)

References 60 publications

(69 reference statements)

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“…Interestingly, apoptosis peaked as early as 24 h after transfer to differentiation medium, indicating that programmed cell death was initiated by differentiation-unrelated factors. This assumption is supported by previous reports on the promoting effect of nicotinamide on cell survival in human pluripotent stem cells [38], on proliferation of aged murine organoids [39] and on inducing apoptosis via reduced intracellular NAD concentrations upon its withdrawal [40]. Taken together, differentiation medium induced apoptosis, thus not supporting long-term culture of canine intestinal organoids.…”

Section: Discussionsupporting

confidence: 56%

Generation of Differentiating and Long-Living Intestinal Organoids Reflecting the Cellular Diversity of Canine Intestine

Kramer

Pratscher

Meneses

et al. 2020

Cells

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Functional intestinal disorders constitute major, potentially lethal health problems in humans. Consequently, research focuses on elucidating the underlying pathobiological mechanisms and establishing therapeutic strategies. In this context, intestinal organoids have emerged as a potent in vitro model as they faithfully recapitulate the structure and function of the intestinal segment they represent. Interestingly, human-like intestinal diseases also affect dogs, making canine intestinal organoids a promising tool for canine and comparative research. Therefore, we generated organoids from canine duodenum, jejunum and colon, and focused on simultaneous long-term expansion and cell differentiation to maximize applicability. Following their establishment, canine intestinal organoids were grown under various culture conditions and then analyzed with respect to cell viability/apoptosis and multi-lineage differentiation by transcription profiling, proliferation assay, cell staining, and transmission electron microscopy. Standard expansion medium supported long-term expansion of organoids irrespective of their origin, but inhibited cell differentiation. Conversely, transfer of organoids to differentiation medium promoted goblet cell and enteroendocrine cell development, but simultaneously induced apoptosis. Unimpeded stem cell renewal and concurrent differentiation was achieved by culturing organoids in the presence of tyrosine kinase ligands. Our findings unambiguously highlight the characteristic cellular diversity of canine duodenum, jejunum and colon as fundamental prerequisite for accurate in vitro modelling.

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Section: Discussionsupporting

confidence: 56%

Generation of Differentiating and Long-Living Intestinal Organoids Reflecting the Cellular Diversity of Canine Intestine

Kramer

Pratscher

Meneses

et al. 2020

Cells

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“…We observed that addition of TGF-beta inhibition induced greater EFTFs expression during early retinal patterning. Nicotinamide was added to the differentiation media (d0-4) to promote the expression of early eye field markers LHX2 and RAX, as previously published [43]. Nicotinamide has been shown to promote cell expansion and adaptation to a radial/rosette morphology.…”

Section: Resultsmentioning

confidence: 99%

Dual SMAD inhibition and Wnt inhibition enable efficient and reproducible differentiations of induced pluripotent stem cells into retinal ganglion cells

Chavali

Haider

Rathi

et al. 2019

Preprint

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Glaucoma is a group of progressive optic neuropathies that share common biological and clinical characteristics including irreversible changes to the optic nerve and visual field loss caused by death of retinal ganglion cells (RGCs). The loss of RGCs manifests as characteristic cupping or optic nerve degeneration, resulting in peripheral vision loss in patients with Glaucoma. Several initial studies carried out RGC differentiation from induced pluripotent stem cells (iPSCs) or embryonic stem cells (ESCs), by modulating classical RGC signaling pathways to mimic in vivo retinal development. Recent studies used small molecules and peptide modulators at specific intervals to fine tune RGC differentiation, and also increase the yields to produce purified RGCs. In this study, we present a chemically defined and functionally novel in vitro methodology for cultivating unprecedented yields of RPC populations from iPSCs, that are then directed toward the RGC lineage. Using this method, we differentiated control iPSC lines into RGCs using in in a stepwise manner using small molecules and peptide modulator treatment to inhibit BMP and TGF-β (SMAD), and canonical Wnt pathways yielding a robust population of iPSC-RGCs. Introduction:

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“…We thought that when PSC was frozen and thawed, simple supplementation with fasudil could significantly improve survival. This effect of fasudil is mediated by the direct inhibition of the ROCK2 intracellular pathway, which is reported to be one of the most important signaling pathways for hPSC survival [52]. Indeed, fasudil dramatically improved cell culturing with hPSC expansion and 3D aggregated suspension.…”

Section: Discussionmentioning

confidence: 99%

The Rho-Associated Kinase Inhibitor Fasudil can Replace Y-27632 for Use in Human Pluripotent Stem Cell Research

So¹,

Lee²,

Park³

et al. 2019

Preprint

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Poor survival of human pluripotent stem cells (hPSCs) following freezing, thawing, or passaging hinders maintenance and differentiation in stem cell research. Rho-associated kinases (ROCKs) play a crucial role in hPSC survival. To date, a typical ROCK inhibitor, Y-27632, has been the primary agent used in hPSC research. Here, we report that another ROCK inhibitor, fasudil, can be used as an alternative. Fasudil increased hPSC growth due to survival rather than proliferation following thawing and passaging, similar to Y-27632. It did not affect pluripotency and genetic integrity including mitochondrial genome (mtDNA). Notably, the genes related to metabolism, mTORC1, and TP53 have mainly displayed a faster recovery pattern with ROCK inhibitors than control. Furthermore, fasudil was confirmed as useful for the single dissociation of hPSCs and for aggregation. It also increased retinal pigment epithelium (RPE) differentiation and the survival of neural crest cells during differentiation. These findings suggest that fasudil can replace Y-27632 for use in stem cell research.

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Nicotinamide Promotes Cell Survival and Differentiation as Kinase Inhibitor in Human Pluripotent Stem Cells

Cited by 75 publications

References 60 publications

Generation of Differentiating and Long-Living Intestinal Organoids Reflecting the Cellular Diversity of Canine Intestine

Generation of Differentiating and Long-Living Intestinal Organoids Reflecting the Cellular Diversity of Canine Intestine

Dual SMAD inhibition and Wnt inhibition enable efficient and reproducible differentiations of induced pluripotent stem cells into retinal ganglion cells

The Rho-Associated Kinase Inhibitor Fasudil can Replace Y-27632 for Use in Human Pluripotent Stem Cell Research

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