cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.16850994.v1
title: Monitoring basal autophagy in the retina utilizing CAG-mRFP-EGFP-MAP1LC3B reporter mouse: technical and biological considerations

description: We describe the utility of a tandem-tagged autophagy reporter mouse model (CAG-RFP-EGFP-MAP1LC3B) in investigating basal macroautophagic/autophagic flux in the neural retina. Western blot, <i>in situ</i> hybridization, immunohistochemistry, and confocal microscopy showed that CAG promoter-driven expression of RFP-EGFP-MAP1LC3B increased “cytosolic” RFP-EGFP-LC3B-I levels, whereas RFP-EGFP-LC3B-II decorates true phagosomes. We verified that the electroretinographic (ERG) responses of tandem-tagged LC3B mice were comparable to those of age-matched controls. Optimized microscope settings detected lipofuscin autofluorescence in retinas of <i>abca4<sup>−/-</sup></i> mice. The majority of retinal phagosomes in the reporter mice exhibited only RFP (not EGFP) fluorescence, suggesting rapid maturation of phagosomes. Only ~1.5% of the total phagosome population was EGFP-labeled; RFP-labeled (mature) phagosomes colocalized with lysosomal markers LAMP2 and CTSD. In the outer retina, phagosome sizes were as follows (in µm<sup>2</sup>, ave ± SEM): RPE, 0.309 ± 0.015; photoreceptor inner segment-myoid, 0.544 ± 0.031; and outer nuclear layer, 0.429 ± 0.011. Detection of RPE phagosomes by fluorescence microscopy is challenging, due to the presence of melanin. Increased lipofuscin autofluorescence, such as observed in the <i>abca4<sup>−/-</sup></i> mouse model of Stargardt disease, is a strong confounding factor when attempting to study autophagy in the RPE. In addition to RPE and photoreceptor cells, phagosomes were detected in inner retinal cell types, microglia, astrocytes, and endothelial cells. We conclude that the tandem-tagged LC3B mouse model serves as a useful system for studying autophagy in the retina. This utility, however, is dependent upon several technical and biological factors, including microscope settings, transgene expression, choice of fluorophores, and lipofuscin autofluorescence. <b>Abbreviations</b>: ACTB: actin, beta; AIF1: allograft inflammatory factor 1; ATG: autophagy related; CTSD: cathepsin D; DAPI: (4’,6-diamido-2-phenylindole); DIC: differential interference contrast; EGFP: enhanced green fluorescent protein; ELM: external limiting membrane; ERG: electroretinography; GCL: ganglion cell layer; GLUL: glutamine-ammonia ligase (glutamine synthetase); INL: inner nuclear layer; IS-E/M: inner segment – ellipsoid/myoid; ISH: <i>in situ hybridization</i>; LAMP2: lysosomal-associated membrane protein 2; L.I.: laser Intensity; MAP1LC3B: microtubule-associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; O.C.T.: optimal cutting temperature; OS: outer segment; ONL: outer nuclear layer; PE: phosphatidylethanolamine; RFP: red fluorescent protein; R.O.I.: region of interest; RPE: retinal pigment epithelium
DOI: 10.6084/m9.figshare.16624335
title: Increased alveolar epithelial TRAF6 via autophagy-dependent TRIM37 degradation mediates particulate matter-induced lung metastasis

description: Epidemiological and clinical studies have shown that exposure to particulate matter (PM) is associated with an increased incidence of lung cancer and metastasis. However, the underlying mechanism remains unclear. Here, we demonstrated the central role of PM-induced neutrophil recruitment in promoting lung cancer metastasis. We found that reactive oxygen species (ROS)-mediated alveolar epithelial macroautophagy/autophagy was essential for initiating neutrophil chemotaxis and pre-metastatic niche formation in the lungs in response to PM exposure. During PM-induced autophagy, the E3 ubiquitin ligase TRIM37 was degraded and protected TRAF6 from proteasomal degradation in lung epithelial cells, which promoted the NFKB-dependent production of chemokines to recruit neutrophils. Importantly, ROS blockade, autophagy inhibition or TRAF6 knockdown abolished PM-induced neutrophil recruitment and lung metastasis enhancement. Our study indicates that host lung epithelial cells and neutrophils coordinate to promote cancer metastasis to the lungs in response to PM exposure and provides ideal therapeutic targets for metastatic progression. <b>Abbreviations</b>: ACTA2/α-SMA: actin alpha 2, smooth muscle, aorta; ATII: alveolar type II; Cho-<i>Traf6</i> siRNA: 5'-cholesterol-<i>Traf6</i> siRNA; EMT: epithelial-mesenchymal transition; HBE: human bronchial epithelial; HCQ: hydroxychloroquine; MAPK: mitogen-activated protein kinase; NAC: N-acetyl-L-cysteine; NFKB: nuclear factor of kappa light polypeptide gene enhancer in B cells; NS: normal saline; PM: particulate matter; ROS: reactive oxygen species; TRAF6: TNF receptor-associated factor 6; TRIM37: tripartite motif-containing 37.
DOI: 10.6084/m9.figshare.16616113
title: MEF2D-NR4A1-FAM134B2-mediated reticulophagy contributes to amino acid homeostasis

description: We recently identified FAM134B2, which is an N-terminal truncated reticulophagy receptor highly induced by starvation such as fasting of mice and treatment of mammalian cells with a starvation medium that does not contain amino acids, glucose and growth factors. However, which starvation signal mediates the induction of FAM134B2 is still obscure. In this study, we found that amino acid deficiency (AAD) could mimic the starvation condition to induce FAM134B2 expression. Unexpectedly, EIF2AK4/GCN2-mediated integrated signal response (ISR) and MTOR (mechanistic target of rapamycin kinase) signals, which constitute two major signaling pathways that respond to AAD, did not contribute to AAD-induced FAM134B2 induction. mRNA-seq and siRNA screenings identified two ISR-independent transcription factors, MEF2D (myocyte enhancer factor 2D) and NR4A1 (nuclear receptor subfamily 4 group A member 1), involved in AAD-induced FAM134B2 expression. AAD induces MEF2D, resulting in the induction of NR4A1, which in turn induces FAM134B2-mediated reticulophagy to maintain intracellular amino acid levels. In conclusion, the MEF2D-NR4A1-FAM134B2 cascade is a critical signal in amino acid homeostasis. AAD: amino acid deficiency; APOC3: apolipoprotein C3; BACH1: BTB domain and CNC homolog 1; CEBP: CCAAT enhancer binding protein; DDIT3/CHOP: DNA damage inducible transcript 3; EBSS: Earle’s Balanced Salt Solution; EIF2AK4/GCN2: eukaryotic translation initiation factor 2 alpha kinase 4; ER: endoplasmic reticulum; HisOH: histidinol; ISR: integrated stress response; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MEF2D: myocyte enhancer factor 2D; MTOR: mechanistic target of rapamycin kinase; NR4A1: nuclear receptor subfamily 4 group A member 1; RETREG1/FAM134B: reticulophagy regulator 1; RTN2: reticulon 2, TF: transcription factor; TFEB: transcription factor EB; ZBTB10: zinc finger and BTB domain containing 10
DOI: 10.6084/m9.figshare.16616113.v2
title: MEF2D-NR4A1-FAM134B2-mediated reticulophagy contributes to amino acid homeostasis

description: We recently identified FAM134B2, which is an N-terminal truncated reticulophagy receptor highly induced by starvation such as fasting of mice and treatment of mammalian cells with a starvation medium that does not contain amino acids, glucose and growth factors. However, which starvation signal mediates the induction of FAM134B2 is still obscure. In this study, we found that amino acid deficiency (AAD) could mimic the starvation condition to induce FAM134B2 expression. Unexpectedly, EIF2AK4/GCN2-mediated integrated signal response (ISR) and MTOR (mechanistic target of rapamycin kinase) signals, which constitute two major signaling pathways that respond to AAD, did not contribute to AAD-induced FAM134B2 induction. mRNA-seq and siRNA screenings identified two ISR-independent transcription factors, MEF2D (myocyte enhancer factor 2D) and NR4A1 (nuclear receptor subfamily 4 group A member 1), involved in AAD-induced FAM134B2 expression. AAD induces MEF2D, resulting in the induction of NR4A1, which in turn induces FAM134B2-mediated reticulophagy to maintain intracellular amino acid levels. In conclusion, the MEF2D-NR4A1-FAM134B2 cascade is a critical signal in amino acid homeostasis. AAD: amino acid deficiency; APOC3: apolipoprotein C3; BACH1: BTB domain and CNC homolog 1; CEBP: CCAAT enhancer binding protein; DDIT3/CHOP: DNA damage inducible transcript 3; EBSS: Earle’s Balanced Salt Solution; EIF2AK4/GCN2: eukaryotic translation initiation factor 2 alpha kinase 4; ER: endoplasmic reticulum; HisOH: histidinol; ISR: integrated stress response; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MEF2D: myocyte enhancer factor 2D; MTOR: mechanistic target of rapamycin kinase; NR4A1: nuclear receptor subfamily 4 group A member 1; RETREG1/FAM134B: reticulophagy regulator 1; RTN2: reticulon 2, TF: transcription factor; TFEB: transcription factor EB; ZBTB10: zinc finger and BTB domain containing 10
DOI: 10.6084/m9.figshare.16624335.v2
title: Increased alveolar epithelial TRAF6 via autophagy-dependent TRIM37 degradation mediates particulate matter-induced lung metastasis

description: Epidemiological and clinical studies have shown that exposure to particulate matter (PM) is associated with an increased incidence of lung cancer and metastasis. However, the underlying mechanism remains unclear. Here, we demonstrated the central role of PM-induced neutrophil recruitment in promoting lung cancer metastasis. We found that reactive oxygen species (ROS)-mediated alveolar epithelial macroautophagy/autophagy was essential for initiating neutrophil chemotaxis and pre-metastatic niche formation in the lungs in response to PM exposure. During PM-induced autophagy, the E3 ubiquitin ligase TRIM37 was degraded and protected TRAF6 from proteasomal degradation in lung epithelial cells, which promoted the NFKB-dependent production of chemokines to recruit neutrophils. Importantly, ROS blockade, autophagy inhibition or TRAF6 knockdown abolished PM-induced neutrophil recruitment and lung metastasis enhancement. Our study indicates that host lung epithelial cells and neutrophils coordinate to promote cancer metastasis to the lungs in response to PM exposure and provides ideal therapeutic targets for metastatic progression. <b>Abbreviations</b>: ACTA2/α-SMA: actin alpha 2, smooth muscle, aorta; ATII: alveolar type II; Cho-<i>Traf6</i> siRNA: 5'-cholesterol-<i>Traf6</i> siRNA; EMT: epithelial-mesenchymal transition; HBE: human bronchial epithelial; HCQ: hydroxychloroquine; MAPK: mitogen-activated protein kinase; NAC: N-acetyl-L-cysteine; NFKB: nuclear factor of kappa light polypeptide gene enhancer in B cells; NS: normal saline; PM: particulate matter; ROS: reactive oxygen species; TRAF6: TNF receptor-associated factor 6; TRIM37: tripartite motif-containing 37.
DOI: 10.6084/m9.figshare.16616113.v1
title: MEF2D-NR4A1-FAM134B2-mediated reticulophagy contributes to amino acid homeostasis

description: We recently identified FAM134B2, which is an N-terminal truncated reticulophagy receptor highly induced by starvation such as fasting of mice and treatment of mammalian cells with a starvation medium that does not contain amino acids, glucose and growth factors. However, which starvation signal mediates the induction of FAM134B2 is still obscure. In this study, we found that amino acid deficiency (AAD) could mimic the starvation condition to induce FAM134B2 expression. Unexpectedly, EIF2AK4/GCN2-mediated integrated signal response (ISR) and MTOR (mechanistic target of rapamycin kinase) signals, which constitute two major signaling pathways that respond to AAD, did not contribute to AAD-induced FAM134B2 induction. mRNA-seq and siRNA screenings identified two ISR-independent transcription factors, MEF2D (myocyte enhancer factor 2D) and NR4A1 (nuclear receptor subfamily 4 group A member 1), involved in AAD-induced FAM134B2 expression. AAD induces MEF2D, resulting in the induction of NR4A1, which in turn induces FAM134B2-mediated reticulophagy to maintain intracellular amino acid levels. In conclusion, the MEF2D-NR4A1-FAM134B2 cascade is a critical signal in amino acid homeostasis.
DOI: 10.6084/m9.figshare.16624335.v1
title: Increased alveolar epithelial TRAF6 via autophagy-dependent TRIM37 degradation mediates particulate matter-induced lung metastasis

description: Epidemiological and clinical studies have shown that exposure to particulate matter (PM) is associated with an increased incidence of lung cancer and metastasis. However, the underlying mechanism remains unclear. Here, we demonstrated the central role of PM-induced neutrophil recruitment in promoting lung cancer metastasis. We found that reactive oxygen species (ROS)-mediated alveolar epithelial macroautophagy/autophagy was essential for initiating neutrophil chemotaxis and pre-metastatic niche formation in the lungs in response to PM exposure. During PM-induced autophagy, the E3 ubiquitin ligase TRIM37 was degraded and protected TRAF6 from proteasomal degradation in lung epithelial cells, which promoted the NFKB-dependent production of chemokines to recruit neutrophils. Importantly, ROS blockade, autophagy inhibition or TRAF6 knockdown abolished PM-induced neutrophil recruitment and lung metastasis enhancement. Our study indicates that host lung epithelial cells and neutrophils coordinate to promote cancer metastasis to the lungs in response to PM exposure and provides ideal therapeutic targets for metastatic progression. <b>Abbreviations</b>: ACTA2/α-SMA: actin alpha 2, smooth muscle, aorta; ATII: alveolar type II; Cho-<i>Traf6</i> siRNA: 5ʹ-cholesterol-<i>Traf6</i> siRNA; EMT: epithelial-mesenchymal transition; HBE: human bronchial epithelial; HCQ: hydroxychloroquine; MAPK: mitogen-activated protein kinase; NAC: N-acetyl-L-cysteine; NFKB: nuclear factor of kappa light polypeptide gene enhancer in B cells; NS: normal saline; PM: particulate matter; ROS: reactive oxygen species; TRAF6: TNF receptor-associated factor 6; TRIM37: tripartite motif-containing 37.
DOI: 10.6084/m9.figshare.16578806
title: Autophagy protects murine preputial glands against premature aging, and controls their sebum phospholipid and pheromone profile

description: Preputial glands are large lipid and hormone secreting sebaceous organs of mice, and present a convenient model for the investigation of biological processes in sebocytes. Suppression of ATG7-dependent macroautophagy/autophagy in epithelial cells of murine skin causes enlargement of hair follicle-associated sebaceous glands and alters the lipid profile of sebum. We have now extended these studies to the preputial glands and find that autophagy significantly delays the onset of age-related ductal ectasia, influences lipid droplet morphology and contributes to the complete dissolution of the mature sebocytes during holocrine secretion. Single cell RNA sequencing showed that many genes involved in lipid metabolism and oxidative stress response were downregulated in immature and mature epithelial cells of ATG7-deficient glands. When analyzing the lipid composition of control and mutant glands, we found that levels of all phospholipid classes, except choline plasmalogen, were decreased in the mutant glands, with a concomitant accumulation of diacyl glycerides. Mass spectrometric imaging (MSI) demonstrated that phospholipid species, specifically the dominant phosphatidylcholine (PC 34:1), were decreased in immature and mature sebocytes. In addition, we found a strong reduction in the amounts of the pheromone, palmityl acetate. Thus, autophagy in the preputial gland is not only important for homeostasis of the gland as a whole and an orderly breakdown of cells during holocrine secretion, but also regulates phospholipid and fatty acid metabolism, as well as pheromone production. ATG7: autophagy related 7; BODIPY: boron dipyrromethene; DAG: diacyl glycerides; DBI: diazepam binding inhibitor; GFP: green fluorescent protein; KRT14: keratin 14; HPLC-MS: high performance liquid chromatography-mass spectrometry; LD: lipid droplet; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MSI: mass spectrometric imaging; ORO: Oil Red O; PC: phosphatidylcholine; PE: phosphatidylethanolamine; PG: preputial gland; PLIN2: perilipin 2; PtdIns: phosphatidylinositol; PL: phospholipids; POPC: 1-palmitoyl-2-oleoyl-PC; PS: phosphatidylserine; qRT-PCR: quantitative reverse transcribed PCR; SG: sebaceous gland; scRNAseq: single-cell RNA sequencing; TAG: triacylglycerides; TLC: thin layer chromatography.
DOI: 10.6084/m9.figshare.16578806.v2
title: Autophagy protects murine preputial glands against premature aging, and controls their sebum phospholipid and pheromone profile

description: Preputial glands are large lipid and hormone secreting sebaceous organs of mice, and present a convenient model for the investigation of biological processes in sebocytes. Suppression of ATG7-dependent macroautophagy/autophagy in epithelial cells of murine skin causes enlargement of hair follicle-associated sebaceous glands and alters the lipid profile of sebum. We have now extended these studies to the preputial glands and find that autophagy significantly delays the onset of age-related ductal ectasia, influences lipid droplet morphology and contributes to the complete dissolution of the mature sebocytes during holocrine secretion. Single cell RNA sequencing showed that many genes involved in lipid metabolism and oxidative stress response were downregulated in immature and mature epithelial cells of ATG7-deficient glands. When analyzing the lipid composition of control and mutant glands, we found that levels of all phospholipid classes, except choline plasmalogen, were decreased in the mutant glands, with a concomitant accumulation of diacyl glycerides. Mass spectrometric imaging (MSI) demonstrated that phospholipid species, specifically the dominant phosphatidylcholine (PC 34:1), were decreased in immature and mature sebocytes. In addition, we found a strong reduction in the amounts of the pheromone, palmityl acetate. Thus, autophagy in the preputial gland is not only important for homeostasis of the gland as a whole and an orderly breakdown of cells during holocrine secretion, but also regulates phospholipid and fatty acid metabolism, as well as pheromone production. ATG7: autophagy related 7; BODIPY: boron dipyrromethene; DAG: diacyl glycerides; DBI: diazepam binding inhibitor; GFP: green fluorescent protein; KRT14: keratin 14; HPLC-MS: high performance liquid chromatography-mass spectrometry; LD: lipid droplet; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MSI: mass spectrometric imaging; ORO: Oil Red O; PC: phosphatidylcholine; PE: phosphatidylethanolamine; PG: preputial gland; PLIN2: perilipin 2; PtdIns: phosphatidylinositol; PL: phospholipids; POPC: 1-palmitoyl-2-oleoyl-PC; PS: phosphatidylserine; qRT-PCR: quantitative reverse transcribed PCR; SG: sebaceous gland; scRNAseq: single-cell RNA sequencing; TAG: triacylglycerides; TLC: thin layer chromatography.
DOI: 10.6084/m9.figshare.16578806.v1
title: Autophagy protects murine preputial glands against premature aging, and controls their sebum phospholipid and pheromone profile

description: Preputial glands are large lipid and hormone secreting sebaceous organs of mice, and present a convenient model for the investigation of biological processes in sebocytes. Suppression of ATG7-dependent macroautophagy/autophagy in epithelial cells of murine skin causes enlargement of hair follicle-associated sebaceous glands and alters the lipid profile of sebum. We have now extended these studies to the preputial glands and find that autophagy significantly delays the onset of age-related ductal ectasia, influences lipid droplet morphology and contributes to the complete dissolution of the mature sebocytes during holocrine secretion. Single cell RNA sequencing showed that many genes involved in lipid metabolism and oxidative stress response were downregulated in immature and mature epithelial cells of ATG7-deficient glands. When analyzing the lipid composition of control and mutant glands, we found that levels of all phospholipid classes, except choline plasmalogen, were decreased in the mutant glands, with a concomitant accumulation of diacyl glycerides. Mass spectrometric imaging (MSI) demonstrated that phospholipid species, specifically the dominant phosphatidylcholine (PC 34:1), were decreased in immature and mature sebocytes. In addition, we found a strong reduction in the amounts of the pheromone, palmityl acetate. Thus, autophagy in the preputial gland is not only important for homeostasis of the gland as a whole and an orderly breakdown of cells during holocrine secretion, but also regulates phospholipid and fatty acid metabolism, as well as pheromone production. <b>Abbreviations</b> ATG7: autophagy related 7; BODIPY: boron dipyrromethene; DAG: diacyl glycerides; DBI: diazepam binding inhibitor; GFP: green fluorescent protein; KRT14: keratin 14; HPLC-MS: high performance liquid chromatography-mass spectrometry; LD: lipid droplet; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MSI: mass spectrometric imaging; ORO: Oil Red O; PC: phosphatidylcholine; PE: phosphatidylethanolamine; PG: preputial gland; PLIN2: perilipin 2; PtdIns: phosphatidylinositol; PL: phospholipids; POPC: 1-palmitoyl-2-oleoyl-PC; PS: phosphatidylserine; qRT-PCR: quantitative reverse transcribed PCR; SG: sebaceous gland; scRNAseq: single-cell RNA sequencing; TAG: triacylglycerides; TLC: thin layer chromatography.
DOI: 10.6084/m9.figshare.19688673
title: Post-transplant cyclophosphamide and sirolimus based graft-versus-host disease prophylaxis after allogeneic stem cell transplantation for acute myeloid leukemia

description: Dataset used for the study "Post-transplant cyclophosphamide and sirolimus based graft-versus-host disease prophylaxis after allogeneic stem cell transplantation for acute myeloid leukemia"
DOI: 10.6084/m9.figshare.19688673.v1
title: Post-transplant cyclophosphamide and sirolimus based graft-versus-host disease prophylaxis after allogeneic stem cell transplantation for acute myeloid leukemia

description: Dataset used for the study "Post-transplant cyclophosphamide and sirolimus based graft-versus-host disease prophylaxis after allogeneic stem cell transplantation for acute myeloid leukemia"
DOI: 10.6084/m9.figshare.20047136.v1
title: Additional file 2 of CBX2 shapes chromatin accessibility promoting AML via p38 MAPK signaling pathway

description: Additional file 2: Supplementary Table 1. List of 223 common genes from comparison between unique regions by ATAC-seq and differentially upregulated (UP_REG DR) genes by RNA-seq in U937 shCBX2 cells. Supplementary Table 2. List of 25 genes included in the GO molecular function kinase binding (FDR q-value = 1.95 e-9). Supplementary Table 3. List of 334 common genes from comparison between unique regions by ATAC-seq and differentially downregulated (DOWN_REG DR) genes by RNA-seq in U937 shCBX2 cells. Supplementary Table 4. GO biological processes of 334 common genes from comparison between unique regions by ATAC-seq and the differentially downregulated (DOWN_REG DR) genes by RNA-seq in U937 shCBX2 cells. Supplementary Table 5. GO Molecular Function of 334 common genes from comparison between unique regions by ATAC-seq and differentially downregulated (DOWN_REG DR) genes by RNA-seq in U937 shCBX2 cells. Supplementary Table 6. GO KEGG pathways of 334 common genes from comparison between unique regions by ATAC-seq and differentially downregulated (DOWN_REG DR) genes by RNA-seq in U937 shCBX2 cells.