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Human cerebral cortex size and complexity has increased greatly during evolution. While increased progenitor diversity and enhanced proliferative potential play important roles in human neurogenesis and gray matter expansion, the mechanisms of human oligodendrogenesis and white matter expansion remain largely unknown. Here, we identify EGFR-expressing “Pre-OPCs” that originate from outer radial glial cells (oRGs) and […]
https://vblwp.azureedge.net/wordpress/2017/09/vbl_logo_no_icon.png00Haig Didizianhttps://vblwp.azureedge.net/wordpress/2017/09/vbl_logo_no_icon.pngHaig Didizian2020-01-01 00:00:002020-01-01 00:00:00Origins and Proliferative States of Human Oligodendrocyte Precursor Cells
Autophagy is essential for cellular survival and energy homeostasis under nutrient deprivation. Despite the emerging importance of nuclear events in autophagy regulation, epigenetic control of autophagy gene transcription remains unclear. Here, we report fasting-induced Fibroblast Growth Factor-21 (FGF21) signaling activates hepatic autophagy and lipid degradation via Jumonji-D3 (JMJD3/KDM6B) histone demethylase. Upon FGF21 signaling, JMJD3 epigenetically […]
Deregulation of mitochondrial network in terminally differentiated cells contributes to a broad spectrum of disorders. Methylmalonic acidemia (MMA) is one of the most common inherited metabolic disorders, due to deficiency of the mitochondrial methylmalonyl-coenzyme A mutase (MMUT). How MMUT deficiency triggers cell damage remains unknown, preventing the development of disease–modifying therapies. Here we combine genetic […]
Mammalian telomeres protect chromosome ends from aberrant DNA repair1. TRF2, a component of the telomere-specific shelterin protein complex, facilitates end protection through sequestration of the terminal telomere repeat sequence within a lariat T-loop structure2,3. Deleting TRF2 (also known as TERF2) in somatic cells abolishes T-loop formation, which coincides with telomere deprotection, chromosome end-to-end fusions and […]
https://vblwp.azureedge.net/wordpress/2017/09/vbl_logo_no_icon.png00Haig Didizianhttps://vblwp.azureedge.net/wordpress/2017/09/vbl_logo_no_icon.pngHaig Didizian2020-01-01 00:00:002020-01-01 00:00:00TRF2-independent chromosome end protection during pluripotency
Fatty acid and triglyceride synthesis increases greatly in response to feeding and insulin. This lipogenic induction involves coordinate transcriptional activation of various enzymes in lipogenic pathway, including fatty acid synthase and glycerol-3-phosphate acyltransferase. Here, we show that JMJD1C is a specific histone demethylase for lipogenic gene transcription in liver. In response to feeding/insulin, JMJD1C is […]
https://vblwp.azureedge.net/wordpress/2017/09/vbl_logo_no_icon.png00Haig Didizianhttps://vblwp.azureedge.net/wordpress/2017/09/vbl_logo_no_icon.pngHaig Didizian2020-01-01 00:00:002020-01-01 00:00:00Histone demethylase JMJD1C is phosphorylated by mTOR to activate de novo lipogenesis
Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-Cov-2) has caused over 5,000,000 cases of Coronavirus disease (COVID-19) with significant fatality rate.1–3 Due to the urgency of this global pandemic, numerous therapeutic and vaccine trials have begun without customary safety and efficacy studies.4 Laboratory mice have been the stalwart of these types of studies; however, they do not […]
https://vblwp.azureedge.net/wordpress/2017/09/vbl_logo_no_icon.png00Haig Didizianhttps://vblwp.azureedge.net/wordpress/2017/09/vbl_logo_no_icon.pngHaig Didizian2020-01-01 00:00:002020-01-01 00:00:00Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling
Brain glucose-sensing neurons detect glucose fluctuations and prevent severe hypoglycemia, but mechanisms mediating functions of these glucose-sensing neurons are unclear. Here we report that estrogen receptor-a (ERa)-expressing neurons in the ventrolateral subdivision of the ventromedial hypothalamic nucleus (vlVMH) can sense glucose fluctuations, being glucose-inhibited neurons (GI-ERavlVMH) or glucose-excited neurons (GE-ERavlVMH). Hypoglycemia activates GI-ERavlVMH neurons via […]
Degeneration of the retinal pigmented epithelium (RPE) and aberrant blood vessel growth in the eye are advanced-stage processes in blinding diseases such as age-related macular degeneration (AMD), which affect hundreds of millions of people worldwide. Loss of the RNase DICER1, an essential factor in micro-RNA biogenesis, is implicated in RPE atrophy. However, the functional implications […]
Origins and Proliferative States of Human Oligodendrocyte Precursor Cells
Human cerebral cortex size and complexity has increased greatly during evolution. While increased progenitor diversity and enhanced proliferative potential play important roles in human neurogenesis and gray matter expansion, the mechanisms of human oligodendrogenesis and white matter expansion remain largely unknown. Here, we identify EGFR-expressing “Pre-OPCs” that originate from outer radial glial cells (oRGs) and […]
Fasting-induced FGF21 signaling activates hepatic autophagy and lipid degradation via JMJD3 histone demethylase
Autophagy is essential for cellular survival and energy homeostasis under nutrient deprivation. Despite the emerging importance of nuclear events in autophagy regulation, epigenetic control of autophagy gene transcription remains unclear. Here, we report fasting-induced Fibroblast Growth Factor-21 (FGF21) signaling activates hepatic autophagy and lipid degradation via Jumonji-D3 (JMJD3/KDM6B) histone demethylase. Upon FGF21 signaling, JMJD3 epigenetically […]
Impaired mitophagy links mitochondrial disease to epithelial stress in methylmalonyl-CoA mutase deficiency
Deregulation of mitochondrial network in terminally differentiated cells contributes to a broad spectrum of disorders. Methylmalonic acidemia (MMA) is one of the most common inherited metabolic disorders, due to deficiency of the mitochondrial methylmalonyl-coenzyme A mutase (MMUT). How MMUT deficiency triggers cell damage remains unknown, preventing the development of disease–modifying therapies. Here we combine genetic […]
TRF2-independent chromosome end protection during pluripotency
Mammalian telomeres protect chromosome ends from aberrant DNA repair1. TRF2, a component of the telomere-specific shelterin protein complex, facilitates end protection through sequestration of the terminal telomere repeat sequence within a lariat T-loop structure2,3. Deleting TRF2 (also known as TERF2) in somatic cells abolishes T-loop formation, which coincides with telomere deprotection, chromosome end-to-end fusions and […]
Histone demethylase JMJD1C is phosphorylated by mTOR to activate de novo lipogenesis
Fatty acid and triglyceride synthesis increases greatly in response to feeding and insulin. This lipogenic induction involves coordinate transcriptional activation of various enzymes in lipogenic pathway, including fatty acid synthase and glycerol-3-phosphate acyltransferase. Here, we show that JMJD1C is a specific histone demethylase for lipogenic gene transcription in liver. In response to feeding/insulin, JMJD1C is […]
Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling
Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-Cov-2) has caused over 5,000,000 cases of Coronavirus disease (COVID-19) with significant fatality rate.1–3 Due to the urgency of this global pandemic, numerous therapeutic and vaccine trials have begun without customary safety and efficacy studies.4 Laboratory mice have been the stalwart of these types of studies; however, they do not […]
Estrogen receptor-a expressing neurons in the ventrolateral VMH regulate glucose balance
Brain glucose-sensing neurons detect glucose fluctuations and prevent severe hypoglycemia, but mechanisms mediating functions of these glucose-sensing neurons are unclear. Here we report that estrogen receptor-a (ERa)-expressing neurons in the ventrolateral subdivision of the ventromedial hypothalamic nucleus (vlVMH) can sense glucose fluctuations, being glucose-inhibited neurons (GI-ERavlVMH) or glucose-excited neurons (GE-ERavlVMH). Hypoglycemia activates GI-ERavlVMH neurons via […]
Chronic Dicer1 deficiency promotes atrophic and neovascular outer retinal pathologies in mice
Degeneration of the retinal pigmented epithelium (RPE) and aberrant blood vessel growth in the eye are advanced-stage processes in blinding diseases such as age-related macular degeneration (AMD), which affect hundreds of millions of people worldwide. Loss of the RNase DICER1, an essential factor in micro-RNA biogenesis, is implicated in RPE atrophy. However, the functional implications […]