Qualitative analysis of mass spectrometry data was performed using the Metware Database (MWDB) constructed based on standard substances. Quantitative analysis was conducted using the Multiple Reaction Monitoring (MRM) mode on a triple quadrupole mass spectrometer.
"],"repository":["MetaboLights"],"study_status":["Public"],"ptm_modification":[""],"instrument_platform":["Liquid Chromatography MS - alternating - hilic","Liquid Chromatography MS - alternating - reverse-phase"],"chromatography_protocol":["T3 method: HPLC column, Waters ACQUITY UPLC HSS T3 C18 (100 mm×2.1 mm i.d.1.8 µm); solvent system, water with 0.05% formic acid (A), acetonitrile with 0.05% formic acid (B). The gradient was started at 5% B (0 min), increased to 95% B (8-9.5 min), finaly ramped back to 5% B (9.6-12 min); flow rate, 0.35 mL/min; temperature, 40°C; injection volume: 2 μL.
Amide method: HPLC: column, ACQUITY UPLC BEH Amide (i.d.2.1×100 mm, 1.7 μm); solvent system, water with 10mM Ammonium acetate and 0.3% Ammonium hydroxide (A), 90% acetonitrile/water (V/V)(B); The gradient was started at 95% B (0-1.2 min), decreased to 70% B (8 min),50% B (9-11 min), finaly ramped back to 95% B (11.1-15 min); flow rate, 0.4 mL/min; temperature, 40°C; injection volume: 2 μL.
"],"publication":["Disruption of Methionine Metabolism Drives Erythroid Cell Fate Reprogramming by Remodeling the H3K4me3 Landscape. 10.1172/jci."],"submitter_affiliation":["Zhengzhou University"],"submitter_name":["Hengchao Zhang"],"organism_part":["erythroblasts"],"technology_type":["mass spectrometry assay"],"disease":[""],"extraction_protocol":["The sample was thawed on ice. 100uL water was added to each sample, vortexed for 2 min. Divide each samples into 2 equal portions, each 50uL, one of which is used for BCA protein quantification.The remaining one sample were added with 200uL pure methanol (precooled at - 20 °C) respectively, vortexed for 2 min under the condition of 2500 r/min.The sample was frozen in liquid nitrogen for 5 min, removed on ice for 5 min, after that, the sample was vortexed for 2 min.The previous step was repeated for 3 times. The sample was centrifuged at 12000 r/min for 10 min at 4°C. Take 190 μL of supernatant into a new centrifuge tube .sonicate in -20°C for 30 min. Then the supernatant was centrifuged at 12000 r/min for 20 min at 4°C. After centrifugation, each sample were divided into 3 equal portions of 60ul supernatant for further LC-MS analysis.
"],"organism":["Homo sapiens"],"full_dataset_link":["https://www.ebi.ac.uk/metabolights/MTBLS10469"],"author":["Chen Lixiang. Aging Decoding and Regeneration Institute; School of Life Sciences, Zhengzhou University,. Science Road 100, Zhengzhou, 450001, China. lxchen@zzu.edu.cn."],"data_transformation_protocol":["The raw MS data were converted to mzml files using ProteoWizard MSConvert software.
"],"study_factor":["Treatment"],"submitter_email":["hengchaoz77@gmail.com"],"sample_collection_protocol":["Human erythroblasts (differentiated from cord blood CD34+ cells) were treated with 0.2 µM DZNep or DMSO (control) for 4 days (from day 7 to day 11 of erythroid differentiation). After treatment, cells were harvested by centrifugation, washed twice with ice-cold phosphate-buffered saline (PBS), and quenched by immersion in liquid nitrogen. The quenched cell pellets were then stored at –80 °C until metabolite extraction. For each sample, three biological replicates were collected.
"],"omics_type":["Metabolomics"],"study_design":["Metabolomics","AB SCIEX QTRAP 6500+","AHCY","erythroblast","3-deazaneplanocin","SCIEX ExionLC AD","targeted analysis","erythroblasts","Homo sapiens","Methylation","experimental control","experimental sample"],"curator_keywords":["Metabolomics","AB SCIEX QTRAP 6500+","erythroblast","AHCY","3-deazaneplanocin","SCIEX ExionLC AD","targeted analysis","erythroblasts","Homo sapiens","Methylation","experimental control","experimental sample"],"mass_spectrometry_protocol":["AB 6500+ QTRAP® LC-MS/MS System, equipped with an ESI Turbo Ion-Spray interface, operating in both positive and negative ion modes and controlled by Analyst 1.6 software (AB Sciex). The ESI source operation parameters were as follows: ion source, turbo spray; source temperature 550°C; ion spray voltage (IS) 5500 V (Positive) ,-4500 V(Neagtive); curtain gas (CUR) were set at 35.0 psi; DP and CE for individual MRM transitions was done with further DP and CE optimization. A specific set of MRM transitions were monitored for each period according to those metabolites eluted within this period.
"],"metabolite_name":["Phe Asn","H-His-Trp-OH","5-methoxyuridine","4-hydroxybenzoic acid","Corticosterone","Phenylacetylglutamine","12-ketolithocholic acid","Denticetic acid","N4-acetyl-2'-O-methylcytidine","N,N-Dimethylguanosine","Lithocholic acid","cis-10-Nonadecenoic acid","Butyric acid","H-Phe-Trp-OH","8-Aminooctanoic acid","2-hydroxyphenylacetic acid","Pantothenol","2-Phospho-D-glyceric acid","L-Leucine","Methylmalonate","5'-deoxyadenosine","5-methoxycarbonylmethyluridine","3-Hydroxyanthranilic Acid","(3,4-Dimethoxyphenyl) Acetic Acid","17alpha-Hydroxypregnenolone","Hydroxyecdysone","2-thio-2'-O-methyluridine","1-Methylxanthine","N2,N2,7-trimethylguanosine","Methyl indole-3-acetate","Hyocholic acid","2-Methylbutyroylcarnitine","Deoxycorticosterone","3-Methyl-1-butylamine","dTMP","Retinoic acid","protocatechuic acid","3-Methoxybenzoic acid","20alpha-Hydroxycholesterol","3-Chloro-L-Tyrosine","4-Hydroxybenzaldehyde","Maslinicacid","Chenodeoxycholic acid 24-acyl-beta-d-glucuronide","4-Methoxy Estrone","Cyclohexylamine","Calcitriol","Decanoyl-carnitine","3-(3-hydroxyphenyl)-3-hydroxypropionic acid","3-Methoxytyramine","3-hydroxyhippuric acid","Dehydrolithocholic acid","Glutaric acid","Octopamine","Alpha-Ketoglutaric Acid","N6,2'-O-dimethyladenosine","Ala-Phe","N-Benzoyl-L-tyrosine ethyl ester","Pregnanediol","24-Hydroxycholesterol","Niacinamide","Myo-Inositol","L-norleucine","Linoleic Acid Amide","Serotonin","Phenylalanine","Cinnabarinic acid","Gallicacid","5-Hydroxylysine","1-Myristoyl-sn-glycero-3-phosphocholine","Allopregnanolone","2-(Formylamino)Benzoic Acid","omega-muricholic acid","Testosterone","17beta-Estradiol","2-Picolinic Acid","Benzoylformic Acid","Oleamide","Cinnamic Acid","3-(2-Hydroxyphenyl)propanoic acid","2-Hydroxyhexadecanoic acid","1H-pyrrole","Hexylamine","2,4-Dihydroxy Benzoic Acid","Pantothenic acid","11-Dehydrocorticosterone","Transvaccenic Acid (C18:1T)","Hexanoyl Glycine","gamma-Glu-Met","Tryptamine","Indolelactic acid","Eudesmic acid","N-Acetylserotonin","Homovanillic Acid","p-Cresol sulfate ammonium salt","4-Methoxyphenylacetic acid","Ursocholic acid","7-Ketocholesterol","4-Acetamidobutyric Acid","3-Hydroxybutyric Acid","Cryptochlorogenic acid","7-methylguanosine","3-beta-deoxycholic acid","Isoallolithocholic acid","3-Oxocholic acid","5-formyl-2'-O-methylcytidine","2-Hydroxydecanoic acid","5,6-Dihydroxyindole-2-Carboxylic Acid","L-Leucic acid","5-iodocytidine","3-hydroxyisovaleric acid","7a,27-Dihydroxycholesterol","Indoleacrylic acid","2-Aminooctanoic acid","Phenaceturic acid","Tyrosine","Hexadecanedioic acid","Potassium Phenyl Sulfate","PYRROLE-2-CARBOXYLIC ACID","Phthalic acid","Phe Val","4-Methoxybenzaldehyde","17a-Estradiol","Gly-Ile","2-Hydroxy Estrone","Nicotinyl Methylamide","Benzenebutyric acid","2-Methoxy Estrone","2-aminobenzoic acid","Dehydroepiandrosterone","L-Thyronine","1,3-Dimethyluric Acid","Ribose-5-phosphate Barium Salt Hydrate","Paraxanthine","Hypoxanthine","Vitamin B9","Chenodeoxycholic acid","Androstenedione","Gly-Trp","Enterodiol","Palmitoyl ethanolamide","Nor-Deoxycholic Acid","O6-methylguanosine","Homogentisic Acid","Hippuric acid","Kynurenic Acid","3-Aminosalicylic acid","Equol","3-Hydroxypicolinic acid","cGMP","Phenylethylamine","Anisic acid","Putrescine","Uracil-5-carboxylic acid","Benzamide","4-thiouridine","Norcholic acid","N6,N6-dimethyladenosine","H-Glu(Leu-OH)-OH","Dihydrotestosterone","3-Methyloxindole","3,4-Dihydroxyphenylacetic Acid","Nicotinuric Acid","Octadecanedioate (C18)","5-Methyluridine","9H-purine","Glycohyodeoxycholic acid","N-Methyltryptamine","Adenosine","S-(5-Adenosy)-L-Homocysteine","7alpha,25-Dihydroxycholesterol","Glutaconic acid","Dodecanoylcarnitine","Dehydroepiandrsterone","L-2-PHENYLGLYCINE","Acetamide","1,5-Diaminopentane","3beta-Hydroxy-5-cholestenoate","1,3,7-Trimethyluric Acid","12,13-DiHOME","Cortisone","N-formylkynurenine","3-Iodo-L-Tyrosine","Fumaric acid","Aceglutamide","Inosine","2-amino-7-methyl-1,7-dihydro-6H-purin-6-one","3-Nitro-L-tyrosine","Isobutyryl-L-carnitine","Lumichrome","Glycolithocholic acid-3-sulfate","Benzoic acid","Melatonin","Glycylphenylalanine","5-METHOXYTRYPTAMINE","5'-Deoxy-5'-methylthioadensine","Cholic acid","Quinolinic Acid","3-hydroxymethylglutaric acid","Pregnenolone","3,3',5-Triiodo-L-Thyronine","N6-threonylcarbamoyladenosine","Phe phe","1-hexadecanoyl-sn-glycero-3-phosphoethanolamine","6-hydroxy melatonin","Histidine","Spermidine","Cortexolone","DL-Mevalonic Acid Lactone","Indole-3-glyoxylic acid","Ethylmalonic acid","Leu-Ala","L-alpha-Aspartyl-L-phenylalanine","1,3-diaminopropane","Ile-Ile","Tyramine","Taurocholic acid","11-Hydroxyandrosterone","Isodeoxycholic acid","Calcifediol","12-Hydroxydodecanoic acid","Gly-Val","5-hydroxyanthranillicacid","beta-muricholic acid","Urocanic acid","Valeric acid","2-Methyllactic acid","gamma-Glu-Phe","N6-methyl-2'-deoxyadenosine","L-Methionine","1-monopalmitoylglycerol","Dihydrouracil","Acetaminophen","Diethyl malonate","3-Indolebutyric Acid","phenol","Methyl dihydrojasmonate","Metanephrine","N6,N6,2'-O-trimethyladenosine","Suberic acid","7-Ketodeoxycholic acid","O-Phospho-L-Serine","Apigenic acid","10Z-Heptadecenoic acid","Guanine","5-Methoxyindole-3-Acetic Acid","2,5-Dihydroxy Benzoic Acid","NADH","Piperine","Sumiki's acid","Bradykinin","3-methyluridine","2-Methoxybenzoic acid","Thyroxine","5,2'-O-dimethyluridine","4-Hydroxy-3-methylbenzoic acid","Kynurenine","Ritalinic acid","N-Acetyl-L-Tyrosine","Xanthurenic Acid","Hydroxyphenyllactic acid","7,12-diketolithocholic acid","L-Pyroglutamic acid","Phe Met","Protocatechuic Aldehyde","Salicylic acid","Taurolithocholic acid","Indole-3-Carboxaldehyde","Levulinic acid","Butylamine","2-thiocytidine","Xanthosine","Tryptophan","7-Hydroxy-cholesten-3-one","3-Methyl-2-oxovaleric acid","Androsterone","2-indolecarboxylic acid","6-Phosphogluconic acid","3-Methylsalicylic acid","17a-Hydroxyprogesterone","L-palmitoylcarnitine","Cyclamic acid","2-Phenylacetamide","Glycolithocholic acid","L-tyrosine methyl ester","Arachidonoyl ethanolamide","Tauro-beta-muricholic acid","Stearoyl-carnitine","Caffeione","2-(3,4-dimethoxyphenyl)ethanamine","7-ketolithocholic acid","trans-aconitic acid","Cortisol","Thymidine","4-Pentenoic acid","Tauroursodeoxycholic acid","3-phenyllactic acid","Aldosterone","Diphenylamine","Glycocholic acid","L-Isoleucine","Indole-3-acetamide","3,5-Diiodo-L-Thyronine","Aniline","2-Amino-3-methoxybenzoic acid","rac Normetanephrine Hydrochloride","4-Hydroxyphenylpyruvic Acid","5-Hydroxy-Tryptophan","3-Phosphoglyceric acid","4-Methylbenzoic acid","Phe Leu","Docosaenoic acid (cis-13)","11-Ketoetiocholanolone","Indole-3-pyruvic acid","3beta-Cholic Acid","Taurohyocholic acid","5-Hydroxyindoleacetic Acid","Caffeicacid","2-hydroxy-2-methylbutyric acid","5-methoxycarbonylmethyl-2-thiouridine","alpha-hexylcinnamaldehyde","Ursolicacid","Tryptophol","6-methyluridine","Propofol Glucuronide","6-Dimethylaminopurine","P-Aminohippuric Acid","Quinoline-2-carboxylic acid","Oxypurinol","5alpha-Pregnane-3,20-dione","Taurochenodeoxycholic acid","Phenoxyacetic acid","1,7-dimethyluric acid","Androstanedione","Isovaleryl-carnitine","2-Piperidone","Isolithocholic acid","2'-O-methyluridine","Octanoyl-carnitine","4-hydroxyhippuric acid","Hexadecanamide","Cyclic-AMP","N-Cyclohexylformamide","2-hydroxyisovaleric Acid","Taurodeoxycholic acid","Taurodehydrocholic acid","Dihydrothymine","P-Aminobenzoate","3-Hydroxytyramine","L-Carnosine","5beta-Androsterone","N-Cinnamylglycine","Dihydrocaffeic acid","16alpha-Hydroxy Estrone","1-Palmitoyl-sn-glycero-3-phosphocholine","Epinephrine","12-Hydroxyoleic acid","3,4-Dihydroxyphenylglycol","3-Phenylpyruvic Acid","Glycochenodeoxycholic acid","Dethiobiotin","2'-O-methylguanosine","Carnosicacid","Oleoylethanolamide","Leu Val","17alpha-Ethinylestradiol","Myristoyl-L-carnitine","Hyodeoxycholic acid","3-oxodeoxycholic acid","Indole-3-carboxylic acid","Glycohyocholic acid","Medroxyprogesterone acetate","Glycodeoxycholic acid","Estrone","Biopterin","Glycodehydrocholic acid","Progesterone","Dopa","beta-indole-3-acetic acid","Pyromucic acid"],"additional_accession":[]},"is_claimable":false,"name":"Disruption of Methionine Metabolism Drives Erythroid Cell Fate Reprogramming by Remodeling the H3K4me3 Landscape","description":"Methionine cycle plays critical roles in cell fate determination by shaping epigenetic landscape, yet its function in human erythropoiesis remains undefined. Here, we show that disruption of methionine metabolism by compromising key enzyme adenosylhomocysteinase (AHCY) reshapes H3K4me3 landscape, causing erythroid cell fate reprogramming. AHCY deficiency severely impaired erythroid differentiation and expansion, leading to the generation of non-erythroid lineage hematopoietic cells, including stem/progenitor cells and immune cells, as evidenced by single-cell RNA sequencing, Pseudo temporal analysis delineated a precise dedifferentiation trajectory, revealing erythroblasts transitioning back to MEPs and HSCs. Moreover, human hematopoietic system could be reconstituted in the immunodeficient NCG-X mice by transplanting AHCY deficient erythroblasts. Mechanistically, AHCY deficiency reduced global H3K4me3 levels and altered its genomic distribution, resulting in the upregulated expression of non-erythroid transcription factors and downregulated expression of erythrocyte lineage-specific transcription factors. Integrated single-cell analyses identified transitional states with diminished AHCY in the erythroblasts of acute myeloid leukemia (AML) patient. Further flow cytometry confirmed the reduced H3K4me3 level in patient derived erythroid cells. Erythroblast isolated from AML patients with reduced H3K4me3 exhibited dedifferentiation potential into progenitor-like states. Our findings reveal a metabolic-epigenetic axis governing cell fate reprogramming in human erythropoiesis and provide insights into leukemia associated anemia.
","dates":{"publication":"2026-06-10","submission":"2026-05-07"},"accession":"MTBLS10469","cross_references":{"KEGG":["Choline","Choline-alfoscerate","Cytosine","Cytidine","Creatinine","Citric-acid","Creatine","Cyclohexylamine","Cinnabarinic-acid","Cholic-acid","Chenodeoxycholic-acid","Chenodeoxycholic-acid-24-acyl-beta-d-glucuronide","Calcifediol","Calcitriol","Caffeione","Cortisone","Cortisol","Cortexolone","Corticosterone","Cyclic-AMP","Cyclamic-acid","Cinnamic-Acid","Caffeicacid","Cryptochlorogenic-acid","Carnosicacid"]}}