Nicotinamide restricts neural precursor proliferation to enhance catecholaminergic neuronal subtype differentiation from mouse embryonic stem cells
Emerging evidence indicates that a strong relationship exists between brain regenerative therapies and nutrition. Early life nutrition plays an important role during embryonic brain development, and there are clear consequences to an imbalance in nutritional factors on both the production and surviv...
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| description | Emerging evidence indicates that a strong relationship exists between brain regenerative therapies and nutrition. Early life nutrition plays an important role during embryonic brain development, and there are clear consequences to an imbalance in nutritional factors on both the production and survival of mature neuronal populations and the infant's risk of diseases in later life. Our research and that of others suggest that vitamins play a fundamental role in the formation of neurons and their survival. There is a growing body of evidence that nicotinamide, the water-soluble amide form of vitamin B.sub.3, is implicated in the conversion of pluripotent stem cells to clinically relevant cells for regenerative therapies. This study investigated the ability of nicotinamide to promote the development of mature catecholaminergic neuronal populations (associated with Parkinson's disease) from mouse embryonic stem cells, as well as investigating the underlying mechanisms of nicotinamide's action. Nicotinamide selectively enhanced the production of tyrosine hydroxylase-expressing neurons and serotonergic neurons from mouse embryonic stem cell cultures (Sox1GFP knock-in 46C cell line). A 5-Ethynyl-2'-deoxyuridine (EdU) assay ascertained that nicotinamide, when added in the initial phase, reduced cell proliferation. Nicotinamide drove tyrosine hydroxylase-expressing neuron differentiation as effectively as an established cocktail of signalling factors, reducing the proliferation of neural progenitors and accelerating neuronal maturation, neurite outgrowth and neurotransmitter expression. These novel findings show that nicotinamide enhanced and enriched catecholaminergic differentiation and inhibited cell proliferation by directing cell cycle arrest in mouse embryonic stem cell cultures, thus driving a critical neural proliferation-to-differentiation switch from neural progenitors to neurons. Further research into the role of vitamin metabolites in embryogenesis will significantly advance cell-based regenerative medicine, and help realize their role as crucial developmental signalling molecules in brain development. |
| doi_str_mv | 10.1371/journal.pone.0233477 |
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Early life nutrition plays an important role during embryonic brain development, and there are clear consequences to an imbalance in nutritional factors on both the production and survival of mature neuronal populations and the infant's risk of diseases in later life. Our research and that of others suggest that vitamins play a fundamental role in the formation of neurons and their survival. There is a growing body of evidence that nicotinamide, the water-soluble amide form of vitamin B.sub.3, is implicated in the conversion of pluripotent stem cells to clinically relevant cells for regenerative therapies. This study investigated the ability of nicotinamide to promote the development of mature catecholaminergic neuronal populations (associated with Parkinson's disease) from mouse embryonic stem cells, as well as investigating the underlying mechanisms of nicotinamide's action. Nicotinamide selectively enhanced the production of tyrosine hydroxylase-expressing neurons and serotonergic neurons from mouse embryonic stem cell cultures (Sox1GFP knock-in 46C cell line). A 5-Ethynyl-2'-deoxyuridine (EdU) assay ascertained that nicotinamide, when added in the initial phase, reduced cell proliferation. Nicotinamide drove tyrosine hydroxylase-expressing neuron differentiation as effectively as an established cocktail of signalling factors, reducing the proliferation of neural progenitors and accelerating neuronal maturation, neurite outgrowth and neurotransmitter expression. These novel findings show that nicotinamide enhanced and enriched catecholaminergic differentiation and inhibited cell proliferation by directing cell cycle arrest in mouse embryonic stem cell cultures, thus driving a critical neural proliferation-to-differentiation switch from neural progenitors to neurons. Further research into the role of vitamin metabolites in embryogenesis will significantly advance cell-based regenerative medicine, and help realize their role as crucial developmental signalling molecules in brain development.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0233477</identifier><identifier>PMID: 32925933</identifier><language>eng</language><publisher>San Francisco: Public Library of Science</publisher><subject>Apoptosis ; Axonogenesis ; Biology and Life Sciences ; Brain ; Catecholamines ; Cell cycle ; Cell differentiation ; Cell proliferation ; Cell survival ; Differentiation ; Dopamine ; Drug dosages ; Embryo cells ; Embryogenesis ; Embryonic growth stage ; Growth ; Health risks ; Hydroxylase ; Maturation ; Medical schools ; Medicine and Health Sciences ; Metabolism ; Metabolites ; Movement disorders ; Neural stem cells ; Neurodegenerative diseases ; Neurogenesis ; Neurons ; Neurotransmitters ; Niacinamide ; Nicotinamide ; Nicotinic acid ; Nutrition ; Nutrition research ; Parkinson's disease ; Physiological aspects ; Pluripotency ; Populations ; Regenerative medicine ; Serotonin ; Signaling ; Stem cell research ; Stem cell transplantation ; Stem cells ; Supervision ; Survival ; Tyrosine ; Tyrosine 3-monooxygenase ; Vitamins</subject><ispartof>PloS one, 2020-09, Vol.15 (9), p.e0233477-e0233477</ispartof><rights>COPYRIGHT 2020 Public Library of Science</rights><rights>2020 Griffin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 Griffin et al 2020 Griffin et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c669t-1b2ddb28af50b1ca383bb3eda2cf33ac8a542c46157f62b1da7a8db3904c5ce43</citedby><cites>FETCH-LOGICAL-c669t-1b2ddb28af50b1ca383bb3eda2cf33ac8a542c46157f62b1da7a8db3904c5ce43</cites><orcidid>0000-0001-8768-510X ; 0000-0002-6670-5084</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489539/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489539/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2103,2929,23868,27926,27927,53793,53795</link.rule.ids></links><search><contributor>Borlongan, Cesar V.</contributor><creatorcontrib>Griffin, Síle M</creatorcontrib><creatorcontrib>Pickard, Mark R</creatorcontrib><creatorcontrib>Hawkins, Clive P</creatorcontrib><creatorcontrib>Williams, Adrian C</creatorcontrib><creatorcontrib>Fricker, Rosemary A</creatorcontrib><title>Nicotinamide restricts neural precursor proliferation to enhance catecholaminergic neuronal subtype differentiation from mouse embryonic stem cells</title><title>PloS one</title><description>Emerging evidence indicates that a strong relationship exists between brain regenerative therapies and nutrition. Early life nutrition plays an important role during embryonic brain development, and there are clear consequences to an imbalance in nutritional factors on both the production and survival of mature neuronal populations and the infant's risk of diseases in later life. Our research and that of others suggest that vitamins play a fundamental role in the formation of neurons and their survival. There is a growing body of evidence that nicotinamide, the water-soluble amide form of vitamin B.sub.3, is implicated in the conversion of pluripotent stem cells to clinically relevant cells for regenerative therapies. This study investigated the ability of nicotinamide to promote the development of mature catecholaminergic neuronal populations (associated with Parkinson's disease) from mouse embryonic stem cells, as well as investigating the underlying mechanisms of nicotinamide's action. Nicotinamide selectively enhanced the production of tyrosine hydroxylase-expressing neurons and serotonergic neurons from mouse embryonic stem cell cultures (Sox1GFP knock-in 46C cell line). A 5-Ethynyl-2'-deoxyuridine (EdU) assay ascertained that nicotinamide, when added in the initial phase, reduced cell proliferation. Nicotinamide drove tyrosine hydroxylase-expressing neuron differentiation as effectively as an established cocktail of signalling factors, reducing the proliferation of neural progenitors and accelerating neuronal maturation, neurite outgrowth and neurotransmitter expression. These novel findings show that nicotinamide enhanced and enriched catecholaminergic differentiation and inhibited cell proliferation by directing cell cycle arrest in mouse embryonic stem cell cultures, thus driving a critical neural proliferation-to-differentiation switch from neural progenitors to neurons. Further research into the role of vitamin metabolites in embryogenesis will significantly advance cell-based regenerative medicine, and help realize their role as crucial developmental signalling molecules in brain development.</description><subject>Apoptosis</subject><subject>Axonogenesis</subject><subject>Biology and Life Sciences</subject><subject>Brain</subject><subject>Catecholamines</subject><subject>Cell cycle</subject><subject>Cell differentiation</subject><subject>Cell proliferation</subject><subject>Cell survival</subject><subject>Differentiation</subject><subject>Dopamine</subject><subject>Drug dosages</subject><subject>Embryo cells</subject><subject>Embryogenesis</subject><subject>Embryonic growth stage</subject><subject>Growth</subject><subject>Health risks</subject><subject>Hydroxylase</subject><subject>Maturation</subject><subject>Medical schools</subject><subject>Medicine and Health 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restricts neural precursor proliferation to enhance catecholaminergic neuronal subtype differentiation from mouse embryonic stem cells</title><author>Griffin, Síle M ; Pickard, Mark R ; Hawkins, Clive P ; Williams, Adrian C ; Fricker, Rosemary A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c669t-1b2ddb28af50b1ca383bb3eda2cf33ac8a542c46157f62b1da7a8db3904c5ce43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Apoptosis</topic><topic>Axonogenesis</topic><topic>Biology and Life Sciences</topic><topic>Brain</topic><topic>Catecholamines</topic><topic>Cell cycle</topic><topic>Cell differentiation</topic><topic>Cell proliferation</topic><topic>Cell survival</topic><topic>Differentiation</topic><topic>Dopamine</topic><topic>Drug dosages</topic><topic>Embryo cells</topic><topic>Embryogenesis</topic><topic>Embryonic growth stage</topic><topic>Growth</topic><topic>Health 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Early life nutrition plays an important role during embryonic brain development, and there are clear consequences to an imbalance in nutritional factors on both the production and survival of mature neuronal populations and the infant's risk of diseases in later life. Our research and that of others suggest that vitamins play a fundamental role in the formation of neurons and their survival. There is a growing body of evidence that nicotinamide, the water-soluble amide form of vitamin B.sub.3, is implicated in the conversion of pluripotent stem cells to clinically relevant cells for regenerative therapies. This study investigated the ability of nicotinamide to promote the development of mature catecholaminergic neuronal populations (associated with Parkinson's disease) from mouse embryonic stem cells, as well as investigating the underlying mechanisms of nicotinamide's action. Nicotinamide selectively enhanced the production of tyrosine hydroxylase-expressing neurons and serotonergic neurons from mouse embryonic stem cell cultures (Sox1GFP knock-in 46C cell line). A 5-Ethynyl-2'-deoxyuridine (EdU) assay ascertained that nicotinamide, when added in the initial phase, reduced cell proliferation. Nicotinamide drove tyrosine hydroxylase-expressing neuron differentiation as effectively as an established cocktail of signalling factors, reducing the proliferation of neural progenitors and accelerating neuronal maturation, neurite outgrowth and neurotransmitter expression. These novel findings show that nicotinamide enhanced and enriched catecholaminergic differentiation and inhibited cell proliferation by directing cell cycle arrest in mouse embryonic stem cell cultures, thus driving a critical neural proliferation-to-differentiation switch from neural progenitors to neurons. Further research into the role of vitamin metabolites in embryogenesis will significantly advance cell-based regenerative medicine, and help realize their role as crucial developmental signalling molecules in brain development.</abstract><cop>San Francisco</cop><pub>Public Library of Science</pub><pmid>32925933</pmid><doi>10.1371/journal.pone.0233477</doi><tpages>e0233477</tpages><orcidid>https://orcid.org/0000-0001-8768-510X</orcidid><orcidid>https://orcid.org/0000-0002-6670-5084</orcidid><oa>free_for_read</oa></addata></record> |
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| issn | 1932-6203 1932-6203 |
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| source | DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Apoptosis Axonogenesis Biology and Life Sciences Brain Catecholamines Cell cycle Cell differentiation Cell proliferation Cell survival Differentiation Dopamine Drug dosages Embryo cells Embryogenesis Embryonic growth stage Growth Health risks Hydroxylase Maturation Medical schools Medicine and Health Sciences Metabolism Metabolites Movement disorders Neural stem cells Neurodegenerative diseases Neurogenesis Neurons Neurotransmitters Niacinamide Nicotinamide Nicotinic acid Nutrition Nutrition research Parkinson's disease Physiological aspects Pluripotency Populations Regenerative medicine Serotonin Signaling Stem cell research Stem cell transplantation Stem cells Supervision Survival Tyrosine Tyrosine 3-monooxygenase Vitamins |
| title | Nicotinamide restricts neural precursor proliferation to enhance catecholaminergic neuronal subtype differentiation from mouse embryonic stem cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-18T02%3A08%3A33IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Nicotinamide%20restricts%20neural%20precursor%20proliferation%20to%20enhance%20catecholaminergic%20neuronal%20subtype%20differentiation%20from%20mouse%20embryonic%20stem%20cells&rft.jtitle=PloS%20one&rft.au=Griffin,%20S%C3%ADle%20M&rft.date=2020-09-14&rft.volume=15&rft.issue=9&rft.spage=e0233477&rft.epage=e0233477&rft.pages=e0233477-e0233477&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0233477&rft_dat=%3Cgale_plos_%3EA635428642%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2442589984&rft_id=info:pmid/32925933&rft_galeid=A635428642&rft_doaj_id=oai_doaj_org_article_d01a960f36534f12baa909cd09bba4f1&rfr_iscdi=true |