Myeloid cell-derived creatine in the hypoxic niche promotes glioblastoma growth
Cell Metab. 2023 Dec 14:S1550-4131(23)00445-X. doi: 10.1016/j.cmet.2023.11.013. Online ahead of print.ABSTRACTGlioblastoma (GBM) is a malignancy dominated by the infiltration of tumor-associated myeloid cells (TAMCs). Examination of TAMC metabolic phenotypes in mouse models and patients with GBM identified the de novo creatine metabolic pathway as a hallmark of TAMCs. Multi-omics analyses revealed that TAMCs surround the hypoxic peri-necrotic regions of GBM and express the creatine metabolic enzyme glycine amidinotransferase (GATM). Conversely, GBM cells located within these same regions are uniquely specific in expressing...
Source: Cell Metabolism - December 22, 2023 Category: Cytology Authors: Aida Rashidi Leah K Billingham Andrew Zolp Tzu-Yi Chia Caylee Silvers Joshua L Katz Cheol H Park Suzi Delay Lauren Boland Yuheng Geng Steven M Markwell Crismita Dmello Victor A Arrieta Kaylee Zilinger Irene M Jacob Aurora Lopez-Rosas David Hou Brandyn Cas Source Type: research
Myeloid cell-derived creatine in the hypoxic niche promotes glioblastoma growth
Cell Metab. 2023 Dec 14:S1550-4131(23)00445-X. doi: 10.1016/j.cmet.2023.11.013. Online ahead of print.ABSTRACTGlioblastoma (GBM) is a malignancy dominated by the infiltration of tumor-associated myeloid cells (TAMCs). Examination of TAMC metabolic phenotypes in mouse models and patients with GBM identified the de novo creatine metabolic pathway as a hallmark of TAMCs. Multi-omics analyses revealed that TAMCs surround the hypoxic peri-necrotic regions of GBM and express the creatine metabolic enzyme glycine amidinotransferase (GATM). Conversely, GBM cells located within these same regions are uniquely specific in expressing...
Source: Cell Metabolism - December 22, 2023 Category: Cytology Authors: Aida Rashidi Leah K Billingham Andrew Zolp Tzu-Yi Chia Caylee Silvers Joshua L Katz Cheol H Park Suzi Delay Lauren Boland Yuheng Geng Steven M Markwell Crismita Dmello Victor A Arrieta Kaylee Zilinger Irene M Jacob Aurora Lopez-Rosas David Hou Brandyn Cas Source Type: research
Myeloid cell-derived creatine in the hypoxic niche promotes glioblastoma growth
Cell Metab. 2023 Dec 14:S1550-4131(23)00445-X. doi: 10.1016/j.cmet.2023.11.013. Online ahead of print.ABSTRACTGlioblastoma (GBM) is a malignancy dominated by the infiltration of tumor-associated myeloid cells (TAMCs). Examination of TAMC metabolic phenotypes in mouse models and patients with GBM identified the de novo creatine metabolic pathway as a hallmark of TAMCs. Multi-omics analyses revealed that TAMCs surround the hypoxic peri-necrotic regions of GBM and express the creatine metabolic enzyme glycine amidinotransferase (GATM). Conversely, GBM cells located within these same regions are uniquely specific in expressing...
Source: Cell Metabolism - December 22, 2023 Category: Cytology Authors: Aida Rashidi Leah K Billingham Andrew Zolp Tzu-Yi Chia Caylee Silvers Joshua L Katz Cheol H Park Suzi Delay Lauren Boland Yuheng Geng Steven M Markwell Crismita Dmello Victor A Arrieta Kaylee Zilinger Irene M Jacob Aurora Lopez-Rosas David Hou Brandyn Cas Source Type: research
Myeloid cell-derived creatine in the hypoxic niche promotes glioblastoma growth
Cell Metab. 2023 Dec 14:S1550-4131(23)00445-X. doi: 10.1016/j.cmet.2023.11.013. Online ahead of print.ABSTRACTGlioblastoma (GBM) is a malignancy dominated by the infiltration of tumor-associated myeloid cells (TAMCs). Examination of TAMC metabolic phenotypes in mouse models and patients with GBM identified the de novo creatine metabolic pathway as a hallmark of TAMCs. Multi-omics analyses revealed that TAMCs surround the hypoxic peri-necrotic regions of GBM and express the creatine metabolic enzyme glycine amidinotransferase (GATM). Conversely, GBM cells located within these same regions are uniquely specific in expressing...
Source: Cell Metabolism - December 22, 2023 Category: Cytology Authors: Aida Rashidi Leah K Billingham Andrew Zolp Tzu-Yi Chia Caylee Silvers Joshua L Katz Cheol H Park Suzi Delay Lauren Boland Yuheng Geng Steven M Markwell Crismita Dmello Victor A Arrieta Kaylee Zilinger Irene M Jacob Aurora Lopez-Rosas David Hou Brandyn Cas Source Type: research
Mitochondrial fatty acid synthesis is an emergent central regulator of mammalian oxidative metabolism
Cell Metab. 2023 Dec 14:S1550-4131(23)00449-7. doi: 10.1016/j.cmet.2023.11.017. Online ahead of print.ABSTRACTContrary to their well-known functions in nutrient breakdown, mitochondria are also important biosynthetic hubs and express an evolutionarily conserved mitochondrial fatty acid synthesis (mtFAS) pathway. mtFAS builds lipoic acid and longer saturated fatty acids, but its exact products, their ultimate destination in cells, and the cellular significance of the pathway are all active research questions. Moreover, why mitochondria need mtFAS despite their well-defined ability to import fatty acids is still unclear. The...
Source: Cell Metabolism - December 21, 2023 Category: Cytology Authors: Riley J Wedan Jacob Z Longenecker Sara M Nowinski Source Type: research
Disrupted RNA editing in beta cells mimics early-stage type 1 diabetes
Cell Metab. 2023 Dec 9:S1550-4131(23)00443-6. doi: 10.1016/j.cmet.2023.11.011. Online ahead of print.ABSTRACTA major hypothesis for the etiology of type 1 diabetes (T1D) postulates initiation by viral infection, leading to double-stranded RNA (dsRNA)-mediated interferon response and inflammation; however, a causal virus has not been identified. Here, we use a mouse model, corroborated with human islet data, to demonstrate that endogenous dsRNA in beta cells can lead to a diabetogenic immune response, thus identifying a virus-independent mechanism for T1D initiation. We found that disruption of the RNA editing enzyme adenos...
Source: Cell Metabolism - December 21, 2023 Category: Cytology Authors: Udi Ehud Knebel Shani Peleg Chunhua Dai Roni Cohen-Fultheim Sara Jonsson Karin Poznyak Maya Israeli Liza Zamashanski Benjamin Glaser Erez Y Levanon Alvin C Powers Agnes Klochendler Yuval Dor Source Type: research
Mitochondrial fatty acid synthesis is an emergent central regulator of mammalian oxidative metabolism
Cell Metab. 2023 Dec 14:S1550-4131(23)00449-7. doi: 10.1016/j.cmet.2023.11.017. Online ahead of print.ABSTRACTContrary to their well-known functions in nutrient breakdown, mitochondria are also important biosynthetic hubs and express an evolutionarily conserved mitochondrial fatty acid synthesis (mtFAS) pathway. mtFAS builds lipoic acid and longer saturated fatty acids, but its exact products, their ultimate destination in cells, and the cellular significance of the pathway are all active research questions. Moreover, why mitochondria need mtFAS despite their well-defined ability to import fatty acids is still unclear. The...
Source: Cell Metabolism - December 21, 2023 Category: Cytology Authors: Riley J Wedan Jacob Z Longenecker Sara M Nowinski Source Type: research
Disrupted RNA editing in beta cells mimics early-stage type 1 diabetes
Cell Metab. 2023 Dec 9:S1550-4131(23)00443-6. doi: 10.1016/j.cmet.2023.11.011. Online ahead of print.ABSTRACTA major hypothesis for the etiology of type 1 diabetes (T1D) postulates initiation by viral infection, leading to double-stranded RNA (dsRNA)-mediated interferon response and inflammation; however, a causal virus has not been identified. Here, we use a mouse model, corroborated with human islet data, to demonstrate that endogenous dsRNA in beta cells can lead to a diabetogenic immune response, thus identifying a virus-independent mechanism for T1D initiation. We found that disruption of the RNA editing enzyme adenos...
Source: Cell Metabolism - December 21, 2023 Category: Cytology Authors: Udi Ehud Knebel Shani Peleg Chunhua Dai Roni Cohen-Fultheim Sara Jonsson Karin Poznyak Maya Israeli Liza Zamashanski Benjamin Glaser Erez Y Levanon Alvin C Powers Agnes Klochendler Yuval Dor Source Type: research
Nutrient inputs and social metabolic control of T cell fate
Cell Metab. 2023 Dec 12:S1550-4131(23)00460-6. doi: 10.1016/j.cmet.2023.12.009. Online ahead of print.ABSTRACTCells in multicellular organisms experience diverse neighbors, signals, and evolving physical environments that drive functional and metabolic demands. To maintain proper development and homeostasis while avoiding inappropriate cell proliferation or death, individual cells interact with their neighbors via "social" cues to share and partition available nutrients. Metabolic signals also contribute to cell fate by providing biochemical links between cell-extrinsic signals and available resources. In addition to metab...
Source: Cell Metabolism - December 20, 2023 Category: Cytology Authors: Zachary A Bacigalupa Madelyn D Landis Jeffrey C Rathmell Source Type: research
Nutrient inputs and social metabolic control of T cell fate
Cell Metab. 2023 Dec 12:S1550-4131(23)00460-6. doi: 10.1016/j.cmet.2023.12.009. Online ahead of print.ABSTRACTCells in multicellular organisms experience diverse neighbors, signals, and evolving physical environments that drive functional and metabolic demands. To maintain proper development and homeostasis while avoiding inappropriate cell proliferation or death, individual cells interact with their neighbors via "social" cues to share and partition available nutrients. Metabolic signals also contribute to cell fate by providing biochemical links between cell-extrinsic signals and available resources. In addition to metab...
Source: Cell Metabolism - December 20, 2023 Category: Cytology Authors: Zachary A Bacigalupa Madelyn D Landis Jeffrey C Rathmell Source Type: research
Apoptosis releases hydrogen sulfide to inhibit Th17 cell differentiation
Cell Metab. 2023 Dec 13:S1550-4131(23)00444-8. doi: 10.1016/j.cmet.2023.11.012. Online ahead of print.ABSTRACTOver 50 billion cells undergo apoptosis each day in an adult human to maintain immune homeostasis. Hydrogen sulfide (H2S) is also required to safeguard the function of immune response. However, it is unknown whether apoptosis regulates H2S production. Here, we show that apoptosis-deficient MRL/lpr (B6.MRL-Faslpr/J) and Bim-/- (B6.129S1-Bcl2l11tm1.1Ast/J) mice exhibit significantly reduced H2S levels along with aberrant differentiation of Th17 cells, which can be rescued by the additional H2S. Moreover, apoptotic ce...
Source: Cell Metabolism - December 19, 2023 Category: Cytology Authors: Qianmin Ou Xinhua Qiao Zhengshi Li Luhan Niu Fangcao Lei Ruifeng Cheng Ting Xie Ning Yang Yao Liu Ling Fu Jing Yang Xueli Mao Xiaoxing Kou Chang Chen Songtao Shi Source Type: research
Targeting gut microbial nitrogen recycling and cellular uptake of ammonium to improve bortezomib resistance in multiple myeloma
This study highlights the specific enrichment of Citrobacter freundii (C. freundii) in patients with relapsed MM. Through fecal microbial transplantation experiments, we demonstrate that C. freundii plays a critical role in inducing drug resistance in MM by increasing levels of circulating ammonium. The ammonium enters MM cells through the transmembrane channel protein SLC12A2, promoting chromosomal instability and drug resistance by stabilizing the NEK2 protein. We show that furosemide sodium, a loop diuretic, downregulates SLC12A2, thereby inhibiting ammonium uptake by MM cells and improving progression-free survival and...
Source: Cell Metabolism - December 19, 2023 Category: Cytology Authors: Yinghong Zhu Xingxing Jian Shuping Chen Gang An Duanfeng Jiang Qin Yang Jingyu Zhang Jian Hu Yi Qiu Xiangling Feng Jiaojiao Guo Xun Chen Zhengjiang Li Ruiqi Zhou Cong Hu Nihan He Fangming Shi Siqing Huang Hong Liu Xin Li Lu Xie Yan Zhu Lia Zhao Yichuan Ji Source Type: research
Central glucagon-like peptide 1 receptor activation inhibits Toll-like receptor agonist-induced inflammation
Cell Metab. 2023 Dec 5:S1550-4131(23)00420-5. doi: 10.1016/j.cmet.2023.11.009. Online ahead of print.ABSTRACTGlucagon-like peptide-1 receptor agonists (GLP-1RAs) exert anti-inflammatory effects relevant to the chronic complications of type 2 diabetes. Although GLP-1RAs attenuate T cell-mediated gut and systemic inflammation directly through the gut intraepithelial lymphocyte GLP-1R, how GLP-1RAs inhibit systemic inflammation in the absence of widespread immune expression of the GLP-1R remains uncertain. Here, we show that GLP-1R activation attenuates the induction of plasma tumor necrosis factor alpha (TNF-α) by multiple ...
Source: Cell Metabolism - December 19, 2023 Category: Cytology Authors: Chi Kin Wong Brent A McLean Laurie L Baggio Jacqueline A Koehler Rola Hammoud Nikolaj Rittig Julian M Yabut Randy J Seeley Theodore J Brown Daniel J Drucker Source Type: research
ChREBP is activated by reductive stress and mediates GCKR-associated metabolic traits
Cell Metab. 2023 Dec 8:S1550-4131(23)00421-7. doi: 10.1016/j.cmet.2023.11.010. Online ahead of print.ABSTRACTCommon genetic variants in glucokinase regulator (GCKR), which encodes GKRP, a regulator of hepatic glucokinase (GCK), influence multiple metabolic traits in genome-wide association studies (GWASs), making GCKR one of the most pleiotropic GWAS loci in the genome. It is unclear why. Prior work has demonstrated that GCKR influences the hepatic cytosolic NADH/NAD+ ratio, also referred to as reductive stress. Here, we demonstrate that reductive stress is sufficient to activate the transcription factor ChREBP and necessa...
Source: Cell Metabolism - December 15, 2023 Category: Cytology Authors: Charandeep Singh Byungchang Jin Nirajan Shrestha Andrew L Markhard Apekshya Panda Sarah E Calvo Amy Deik Xingxiu Pan Austin L Zuckerman Amel Ben Saad Kathleen E Corey Julia Sjoquist Stephanie Osganian Roya AminiTabrizi Eugene P Rhee Hardik Shah Olga Goldb Source Type: research
ChREBP is activated by reductive stress and mediates GCKR-associated metabolic traits
Cell Metab. 2023 Dec 8:S1550-4131(23)00421-7. doi: 10.1016/j.cmet.2023.11.010. Online ahead of print.ABSTRACTCommon genetic variants in glucokinase regulator (GCKR), which encodes GKRP, a regulator of hepatic glucokinase (GCK), influence multiple metabolic traits in genome-wide association studies (GWASs), making GCKR one of the most pleiotropic GWAS loci in the genome. It is unclear why. Prior work has demonstrated that GCKR influences the hepatic cytosolic NADH/NAD+ ratio, also referred to as reductive stress. Here, we demonstrate that reductive stress is sufficient to activate the transcription factor ChREBP and necessa...
Source: Cell Metabolism - December 15, 2023 Category: Cytology Authors: Charandeep Singh Byungchang Jin Nirajan Shrestha Andrew L Markhard Apekshya Panda Sarah E Calvo Amy Deik Xingxiu Pan Austin L Zuckerman Amel Ben Saad Kathleen E Corey Julia Sjoquist Stephanie Osganian Roya AminiTabrizi Eugene P Rhee Hardik Shah Olga Goldb Source Type: research
