Cholesterol biosynthesis modulates differentiation in murine cranial neural crest cells.
Cholesterol biosynthesis modulates differentiation in murine cranial neural crest cells.
复制标题
DOI：
10.1038/s41598-023-32922-9
复制
发表时间：
2023-05-01
影响因子：
4.6
通讯作者：
Shaw, Natalie D.
中科院分区：
文献类型：
--
作者：
Pascual, Florencia;Icyuz, Mert;Karmaus, Peer;Brooks, Ashley;Van Gorder, Elizabeth;Fessler, Michael B.;Shaw, Natalie D.
颅神经嵴细胞（cNCC）是一种多能胚胎细胞群，可产生多种细胞类型。这些细胞特别容易受到外部代谢应激因素的影响，例如母体高血糖和先天性畸形之间的关联。我们感兴趣的是使用已建立的鼠神经嵴细胞模型（O 9 -1）研究不同浓度的葡萄糖和丙酮酸对cNCC代谢、迁移和分化的影响。我们出乎意料地观察到一种模式的基因表达提示胆固醇生物合成诱导下的葡萄糖耗竭条件下的O 9 -1细胞。我们进一步表明，两种不同的胆固醇合成抑制剂的治疗干扰细胞迁移和分化，抑制软骨形成，同时增强平滑肌细胞分化。由于先天性无鼻症（缺少外鼻），SMCHD 1突变引起的畸形，似乎部分代表了cNCC的缺陷，我们也有兴趣研究葡萄糖和胆固醇的可用性对O 9 -1细胞中Smchd 1表达的影响。Smchd 1的表达在高糖条件下诱导，而胆固醇合成抑制剂降低Smchd 1的表达在软骨形成。这些数据突出了胆固醇生物合成在cNCC生理学中的新作用，并表明SMCHD 1突变携带者的人类表型变异性可能部分与SMCHD 1在发育过程中对葡萄糖或胆固醇剂量的敏感性有关。
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.
登录
查看更多内容
影响因子：
5.8
作者：
Kubota, T;Fujisaki, K;Oishi, R
通讯作者：
Oishi, R
影响因子：
2
作者：
Graham, JM;Lee, J
通讯作者：
Lee, J
影响因子：
4.8
作者：
Gholkar, Ankur A.;Cheung, Keith;Torres, Jorge Z.
通讯作者：
Torres, Jorge Z.
影响因子：
3.6
作者：
HAUGUEL, S;DESMAIZIERES, V;CHALLIER, JC
通讯作者：
CHALLIER, JC
通过荧光检测caspase激活来连续监测凋亡的一种可访问且高通量的策略。
影响因子：
2.9
作者：
Hanson KM;Finkelstein JN
通讯作者：
Finkelstein JN