Evidence map›Paper›PMID 38701782›Full record

ArticleCell2024

Small-molecule-induced epigenetic rejuvenation promotes SREBP condensation and overcomes barriers to CNS myelin regeneration.

Xuezhao Liu, Dazhuan Eric Xin, Xiaowen Zhong, Chuntao Zhao, Zhidan Li, Liguo Zhang, Adam J Dourson, Lindsay Lee, Shreya Mishra, Arman E Bayat and 24 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

43 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

34 authors.

Xuezhao LiuDepartment of Pediatrics, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Dazhuan Eric XinDepartment of Pediatrics, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Xiaowen ZhongDepartment of Pediatrics, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, Ohio, 45229, USA.
Chuntao ZhaoDepartment of Pediatrics, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Zhidan LiCenter for Translational Medicine, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, P.R. China.
Liguo ZhangDepartment of Pediatrics, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Adam J DoursonDepartment of Anesthesia, Division of Pain Management, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Lindsay LeeDepartment of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic Foundation, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Shreya MishraDepartment of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic Foundation, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Arman E BayatDepartment of Pediatrics, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Eva NicholsonDepartment of Pediatrics, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
William L SeibelDepartment of Pediatrics, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Bingfang YanDivision of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, Ohio, 45229, USA.
Joel MasonFlorey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne 3052, Australia.
Bradley J TurnerFlorey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne 3052, Australia.
David G GonsalvezDepartment of Anatomy and Developmental Biology, Monash University, Melbourne 3168, Australia.
William OngSchool of Chemistry, Chemical Engineering, and Biotechnology Nanyang Technological University, Singapore 637459, Singapore.
Sing Yian ChewSchool of Chemistry, Chemical Engineering, and Biotechnology Nanyang Technological University, Singapore 637459, Singapore; Lee Kong Chian School of Medicine, School of Materials Science and Engineering, Nanyang Technological University, Singapore 639798, Singapore.
Balaram GhoshEpigenetic Research Laboratory, Department of Pharmacy, Birla Institute of Technology and Science-Pilani Hyderabad Campus, Shamirpet, Hyderabad, India, 500078.
Sung Ok YoonDepartment of Biological Chemistry and Pharmacology, Ohio State University, Columbus, Ohio.
Mei XinDepartment of Pediatrics, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Zhigang HeF.M. Kirby Neurobiology Center, Boston Children's Hospital, and Department of Neurology and Ophthalmology, Harvard Medical School, Boston, MA, USA.
Jason TchieuDepartment of Pediatrics, Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Michael WegnerInstitut für Biochemie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
Klaus-Armin NaveDepartment of Neurogenetics, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
Robin J M FranklinAltos Labs, Cambridge Institute of Science, Granta Park, Cambridge CB21 6GP, UK.
Ranjan DuttaDepartment of Neurosciences, Lerner Research Institute, Cleveland Clinic, Case Western Reserve University School of Medicine, Cleveland, OH 44195, USA.
Bruce D TrappDepartment of Neurosciences, Lerner Research Institute, Cleveland Clinic, Case Western Reserve University School of Medicine, Cleveland, OH 44195, USA.
Ming HuDepartment of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic Foundation, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Matthew A SmithDepartment of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, OH, USA; Rebecca D. Considine Research Institute, Akron Children's Hospital, Akron, OH, USA.
Michael P JankowskiDepartment of Anesthesia, Division of Pain Management, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Pediatric Pain Research Center, Cincinnati Children's Hospital, Cincinnati, OH, USA.
Samantha K BartonFlorey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne 3052, Australia.
Xuelian HeCenter for Translational Medicine, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, P.R. China. Electronic address: Xuelian_he2021@scu.edu.cn.
Q Richard LuDepartment of Pediatrics, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. Electronic address: Richard.lu@cchmc.org.

Funding

Genetic Analysis and Manipulation Core (GAEC)P50HD105351 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI Hisashi Umemori · 2021 to 2026
$9.4M
Pathogenesis of Neurological Disability in Primary Diseases of MyelinR35NS097303 · NINDS · CLEVELAND CLINIC LERNER COM-CWRU · PI TRAPP, BRUCE D · 2017 to 2024
$6.9M
Therapeutic and mechanistic significance of altered metabolism of HIV medicines by alcohol- or alcohol/synthetic opioid combinationR01AA030486 · NIAAA · UNIVERSITY OF CINCINNATI · PI JASON T BLACKARD, Jennifer L Brown · 2022 to 2026
$3.5M
Sensitization of developing sensory neurons after incisionR01NS105715 · NINDS · CINCINNATI CHILDRENS HOSP MED CTR · PI Michael P Jankowski · 2019 to 2026
$3.3M
Mechanisms of muscle afferent sensitization after ischemiaR01NS113965 · NINDS · CINCINNATI CHILDRENS HOSP MED CTR · PI JANKOWSKI, MICHAEL P · 2020 to 2024
$2.4M
Metabolism-based interactions and organ-targeted delivery of molnupiravir, nirmatrelvir and remdesivirR01AI172959 · NIAID · UNIVERSITY OF CINCINNATI · PI Bingfang Yan · 2023 to 2026
$2.0M
NIAAA NIH HHS R01 AA030486NIAID NIH HHS R01 AI172959NICHD NIH HHS P50 HD105351NINDS NIH HHS R01 NS105715NINDS NIH HHS R01 NS113965NINDS NIH HHS R35 NS097303
6 · The paper itself

Abstract

Remyelination failure in diseases like multiple sclerosis (MS) was thought to involve suppressed maturation of oligodendrocyte precursors; however, oligodendrocytes are present in MS lesions yet lack myelin production. We found that oligodendrocytes in the lesions are epigenetically silenced. Developing a transgenic reporter labeling differentiated oligodendrocytes for phenotypic screening, we identified a small-molecule epigenetic-silencing-inhibitor (ESI1) that enhances myelin production and ensheathment. ESI1 promotes remyelination in animal models of demyelination and enables de novo myelinogenesis on regenerated CNS axons. ESI1 treatment lengthened myelin sheaths in human iPSC-derived organoids and augmented (re)myelination in aged mice while reversing age-related cognitive decline. Multi-omics revealed that ESI1 induces an active chromatin landscape that activates myelinogenic pathways and reprograms metabolism. Notably, ESI1 triggered nuclear condensate formation of master lipid-metabolic regulators SREBP1/2, concentrating transcriptional co-activators to drive lipid/cholesterol biosynthesis. Our study highlights the potential of targeting epigenetic silencing to enable CNS myelin regeneration in demyelinating diseases and aging.

Indexed as

Epigenesis, GeneticMyelin SheathOligodendrogliaRemyelinationAnimalsCell DifferentiationCentral Nervous SystemDemyelinating DiseasesHumansInduced Pluripotent Stem CellsMaleMiceMice, Inbred C57BLMultiple SclerosisOrganoidsRegenerationSmall Molecule LibrariesSterol Regulatory Element Binding Protein 1agingchromatin remodelingEpigenetic silencingHDAC3 Inhibitionlipid/cholesterol biosynthesismultiple sclerosismyelin regenerationoligodendrocytesmall moleculeSREBP condensation

Identifiers

PMID38701782
PMCPMC11812128

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.