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Cholesterol biosynthesis modulates differentiation in murine cranial neural crest cells

Cranial neural crest cells (cNCC) are a multipotent embryonic cell population that give rise to a diverse set of cell types. These cells are particularly vulnerable to external metabolic stressors, as exemplified by the association between maternal hyperglycemia and congenital malformations. We were...

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Autores principales: Pascual, Florencia, Icyuz, Mert, Karmaus, Peer, Brooks, Ashley, Van Gorder, Elizabeth, Fessler, Michael B., Shaw, Natalie D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10151342/
https://www.ncbi.nlm.nih.gov/pubmed/37127649
http://dx.doi.org/10.1038/s41598-023-32922-9
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author Pascual, Florencia
Icyuz, Mert
Karmaus, Peer
Brooks, Ashley
Van Gorder, Elizabeth
Fessler, Michael B.
Shaw, Natalie D.
author_facet Pascual, Florencia
Icyuz, Mert
Karmaus, Peer
Brooks, Ashley
Van Gorder, Elizabeth
Fessler, Michael B.
Shaw, Natalie D.
author_sort Pascual, Florencia
collection PubMed
description Cranial neural crest cells (cNCC) are a multipotent embryonic cell population that give rise to a diverse set of cell types. These cells are particularly vulnerable to external metabolic stressors, as exemplified by the association between maternal hyperglycemia and congenital malformations. We were interested in studying the effect of various concentrations of glucose and pyruvate on cNCC metabolism, migration, and differentiation using an established murine neural crest cell model (O9-1). We unexpectedly observed a pattern of gene expression suggestive of cholesterol biosynthesis induction under glucose depletion conditions in O9-1 cells. We further showed that treatment with two different cholesterol synthesis inhibitors interfered with cell migration and differentiation, inhibiting chondrogenesis while enhancing smooth muscle cell differentiation. As congenital arhinia (absent external nose), a malformation caused by mutations in SMCHD1, appears to represent, in part, a defect in cNCC, we were also interested in investigating the effects of glucose and cholesterol availability on Smchd1 expression in O9-1 cells. Smchd1 expression was induced under high glucose conditions whereas cholesterol synthesis inhibitors decreased Smchd1 expression during chondrogenesis. These data highlight a novel role for cholesterol biosynthesis in cNCC physiology and demonstrate that human phenotypic variability in SMCHD1 mutation carriers may be related, in part, to SMCHD1’s sensitivity to glucose or cholesterol dosage during development.
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spelling pubmed-101513422023-05-03 Cholesterol biosynthesis modulates differentiation in murine cranial neural crest cells Pascual, Florencia Icyuz, Mert Karmaus, Peer Brooks, Ashley Van Gorder, Elizabeth Fessler, Michael B. Shaw, Natalie D. Sci Rep Article Cranial neural crest cells (cNCC) are a multipotent embryonic cell population that give rise to a diverse set of cell types. These cells are particularly vulnerable to external metabolic stressors, as exemplified by the association between maternal hyperglycemia and congenital malformations. We were interested in studying the effect of various concentrations of glucose and pyruvate on cNCC metabolism, migration, and differentiation using an established murine neural crest cell model (O9-1). We unexpectedly observed a pattern of gene expression suggestive of cholesterol biosynthesis induction under glucose depletion conditions in O9-1 cells. We further showed that treatment with two different cholesterol synthesis inhibitors interfered with cell migration and differentiation, inhibiting chondrogenesis while enhancing smooth muscle cell differentiation. As congenital arhinia (absent external nose), a malformation caused by mutations in SMCHD1, appears to represent, in part, a defect in cNCC, we were also interested in investigating the effects of glucose and cholesterol availability on Smchd1 expression in O9-1 cells. Smchd1 expression was induced under high glucose conditions whereas cholesterol synthesis inhibitors decreased Smchd1 expression during chondrogenesis. These data highlight a novel role for cholesterol biosynthesis in cNCC physiology and demonstrate that human phenotypic variability in SMCHD1 mutation carriers may be related, in part, to SMCHD1’s sensitivity to glucose or cholesterol dosage during development. Nature Publishing Group UK 2023-05-01 /pmc/articles/PMC10151342/ /pubmed/37127649 http://dx.doi.org/10.1038/s41598-023-32922-9 Text en © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Pascual, Florencia
Icyuz, Mert
Karmaus, Peer
Brooks, Ashley
Van Gorder, Elizabeth
Fessler, Michael B.
Shaw, Natalie D.
Cholesterol biosynthesis modulates differentiation in murine cranial neural crest cells
title Cholesterol biosynthesis modulates differentiation in murine cranial neural crest cells
title_full Cholesterol biosynthesis modulates differentiation in murine cranial neural crest cells
title_fullStr Cholesterol biosynthesis modulates differentiation in murine cranial neural crest cells
title_full_unstemmed Cholesterol biosynthesis modulates differentiation in murine cranial neural crest cells
title_short Cholesterol biosynthesis modulates differentiation in murine cranial neural crest cells
title_sort cholesterol biosynthesis modulates differentiation in murine cranial neural crest cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10151342/
https://www.ncbi.nlm.nih.gov/pubmed/37127649
http://dx.doi.org/10.1038/s41598-023-32922-9
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