Similar Datasets
Project description:Cells change their metabolic profiles in response to underlying gene regulatory networks, but how can alterations in metabolism encode specific transcriptional instructions? Here, we show that forcing a metabolic change in embryonic stem cells (ESCs) promotes a developmental identity that better approximates the inner cell mass (ICM) of the early mammalian blastocyst in cultures. This shift in cellular identity depends on inhibition of glycolysis and stimulation of oxidative phosphorylation (OXPHOS) triggered by replacement of D-glucose by D-galactose in ESC media. Enhanced OXPHOS in turn activates NAD+-dependent deacetylases of the sirtuin family, resulting in deacetylation of histones and key transcription factors to focus enhancer activity while reducing transcriptional noise, that result in a robustly enhanced ESC phenotype. This exploitation of a NAD+/NADH coenzyme coupled to OXPHOS as a means of programming lineage-specific transcription suggests new paradigms for how cells respond to alterations in their environment, and implies cellular rejuvenation exploits enzymatic activities for simultaneous activation of a discrete enhancer set alongside silencing genome-wide transcriptional noise.
| S-SCDT-10_1038-S44318-025-00417-0 | biostudies-other
Project description:Cells change their metabolic profiles in response to an underling gene regulatory network, but how can alterations in metabolism encode specific transcriptional instructions? Here we show that forcing metabolic change in embryonic stem cells (ESCs) promotes a developmental identity that better approximates the inner cell mass (ICM) of the mammalian blastocyst in cultures we refer to as enhanced metabolic ESCs (EMESCs). The creation of EMESCs depends on the inhibition of glycolysis and stimulation of oxidative phosphorylation (OXPHOS), that in turns activates NAD+-dependent deacetlylases of the Sirtuin family. The activation of this pathway leads to the deacetylation of histones and key transcription factors leading to a revised ICM-like gene regulatory network. The exploitation of the NAD+/NADH coenzyme normally coupled to elevated OXPHOS to program lineage specific transcription suggests new paradigms for how cells respond to alterations in their environment.
2025-04-01 | GSE173542 | GEO
Project description:Cells change their metabolic profiles in response to an underling gene regulatory network, but how can alterations in metabolism encode specific transcriptional instructions? Here we show that forcing metabolic change in embryonic stem cells (ESCs) promotes a developmental identity that better approximates the inner cell mass (ICM) of the mammalian blastocyst in cultures we refer to as enhanced metabolic ESCs (EMESCs). The creation of EMESCs depends on the inhibition of glycolysis and stimulation of oxidative phosphorylation (OXPHOS), that in turns activates NAD+-dependent deacetlylases of the Sirtuin family. The activation of this pathway leads to the deacetylation of histones and key transcription factors leading to a revised ICM-like gene regulatory network. The exploitation of the NAD+/NADH coenzyme normally coupled to elevated OXPHOS to program lineage specific transcription suggests new paradigms for how cells respond to alterations in their environment.
2025-04-01 | GSE173532 | GEO
Project description:Cells change their metabolic profiles in response to an underling gene regulatory network, but how can alterations in metabolism encode specific transcriptional instructions? Here we show that forcing metabolic change in embryonic stem cells (ESCs) promotes a developmental identity that better approximates the inner cell mass (ICM) of the mammalian blastocyst in cultures we refer to as enhanced metabolic ESCs (EMESCs). The creation of EMESCs depends on the inhibition of glycolysis and stimulation of oxidative phosphorylation (OXPHOS), that in turns activates NAD+-dependent deacetlylases of the Sirtuin family. The activation of this pathway leads to the deacetylation of histones and key transcription factors leading to a revised ICM-like gene regulatory network. The exploitation of the NAD+/NADH coenzyme normally coupled to elevated OXPHOS to program lineage specific transcription suggests new paradigms for how cells respond to alterations in their environment.
2025-04-30 | PXD025468 | Pride
Project description:Altering metabolism to program cell identity via NAD+ dependent deacetylation
| PRJNA726042 | ENA
Project description:Cells change their metabolic profiles in response to underlying gene regulatory networks, but how can alterations in metabolism encode specific transcriptional instructions? Here, we show that forcing a metabolic change in embryonic stem cells (ESCs) promotes a developmental identity that better approximates the inner cell mass (ICM) of the early mammalian blastocyst in cultures we refer to as enhanced metabolic ESCs (EMESCs). The creation of EMESCs depends on inhibition of glycolysis and stimulation of oxidative phosphorylation (OXPHOS), that in turns activates NAD+-dependent deacetylases of the Sirtuin family, resulting in the deacetylation of histones and key transcription factors to focus enhancer activity while reducing transcriptional noise, that result in a robust enhanced ESC phenotype. This exploitation of a NAD+/NADH coenzyme coupled to OXPHOS as a means of programming lineage specific transcription suggests new paradigms for how cells respond to alterations in their environment, and implies cellular rejuvenation exploits enzymatic activities to for simultaneous activation of a discrete enhancer set alongside silencing genome-wide transcriptional noise.
2025-04-01 | GSE252342 | GEO
Project description:Altering metabolism to program cell identity via NAD+ dependent deacetylation [RNA-seq]
| PRJNA725905 | ENA
Project description:Altering metabolism to program cell identity via NAD+ dependent deacetylation [ATAC-seq]
| PRJNA726044 | ENA
Project description:Altering metabolism programs cell identity via NAD+-dependent deacetylation [CUT&Tag]
| PRJNA1060259 | ENA
Project description:This study investigated the effect of nicotinamide (NAM) supplementation on the development of brain inflammation and microglial activation in a mouse model of type 1 diabetes mellitus. C57BL/6J male mice, which were made diabetic with five consecutive, low-dose (55 mg/kg i.p.) streptozotocin (STZ) injections. Diabetic mice were randomly distributed in different experimental groups and challenged to different doses of NAM (untreated, NAM low-dose, LD, 0.1%; NAM high-dose, HD, 0.25%) for 25 days. A control, non-diabetic group of mice was used as a reference. The NAD+ content was increased in the brains of NAM-treated mice compared with untreated diabetic mice (NAM LD: 3-fold; NAM HD: 3-fold, p-value < 0.05). Immunohistochemical staining revealed that markers of inflammation (TNFα: NAM LD: -35%; NAM HD: -46%; p-value < 0.05) and microglial activation (IBA-1: NAM LD: -29%; NAM HD: -50%; p-value < 0.05; BDKRB1: NAM LD: -36%; NAM HD: -37%; p-value < 0.05) in brains from NAM-treated diabetic mice were significantly decreased compared with non-treated T1D mice. This finding was accompanied by a concomitant alleviation of nuclear NFκB (p65) signaling in treated diabetic mice (NFκB (p65): NAM LD: -38%; NAM HD: -53%, p-value < 0.05). Notably, the acetylated form of the nuclear NFκB (p65) was significantly decreased in the brains of NAM-treated, diabetic mice (NAM LD: -48%; NAM HD: -63%, p-value < 0.05) and inversely correlated with NAD+ content (r = -0.50, p-value = 0.03), suggesting increased activity of NAD+-dependent deacetylases in the brains of treated mice. Thus, dietary NAM supplementation in diabetic T1D mice prevented brain inflammation via NAD+-dependent deacetylation mechanisms, suggesting an increased action of sirtuin signaling.
| S-EPMC10383777 | biostudies-literature