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Article: Comparative dose effectiveness of intravenous and intrathecal AAV9.CB7.hIDS, RGX-121, in mucopolysaccharidosis type II mice.

Smith, Miles C / Belur, Lalitha R / Karlen, Andrea D / Erlanson, Olivia / Furcich, Justin / Lund, Troy C / Seelig, Davis / Kitto, Kelley F / Fairbanks, Carolyn A / Kim, Kwi Hye / Buss, Nick / McIvor, R Scott

Molecular therapy. Methods & clinical development

2024 Volume 32, Issue 1, Page(s) 101201

Abstract: Mucopolysaccharidosis type II (MPS II) is an X-linked recessive lysosomal disease caused by iduronate-2-sulfatase (IDS) deficiency, leading to accumulation of glycosaminoglycans (GAGs) and the emergence of progressive disease. Enzyme replacement therapy ... ...

Abstract	Mucopolysaccharidosis type II (MPS II) is an X-linked recessive lysosomal disease caused by iduronate-2-sulfatase (IDS) deficiency, leading to accumulation of glycosaminoglycans (GAGs) and the emergence of progressive disease. Enzyme replacement therapy is the only currently approved treatment, but it leaves neurological disease unaddressed. Cerebrospinal fluid (CSF)-directed administration of AAV9.CB7.hIDS (RGX-121) is an alternative treatment strategy, but it is unknown if this approach will affect both neurologic and systemic manifestations. We compared the effectiveness of intrathecal (i.t.) and intravenous (i.v.) routes of administration (ROAs) at a range of vector doses in a mouse model of MPS II. While lower doses were completely ineffective, a total dose of 1 × 10
Language	English
Publishing date	2024-01-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	2872938-9
ISSN	2329-0501 ; 2329-0501
ISSN (online)	2329-0501
ISSN	2329-0501
DOI	10.1016/j.omtm.2024.101201
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Article: Exploring the experiences and perspectives of emergency physicians on brain death organ tissue donation after the Life-Sustaining Treatment Decision Act.

Park, Song Yi / Kim, Hyun / Park, Kwi Hwa / Park, Seung Min / Lee, Dong Eun / Jung, Yong Hun / Jeong, Wonjoon / Park, Kyung Hye

Korean journal of transplantation

2022 Volume 36, Issue 1, Page(s) 29–36

Abstract: Background: This study explored emergency physicians' experiences and perspectives related to brain death organ tissue donation (OTD) after the enforcement of the Life-Sustaining Treatment (LST) Decision Act in Korea.: Methods: Using the Braun and ... ...

Abstract	Background: This study explored emergency physicians' experiences and perspectives related to brain death organ tissue donation (OTD) after the enforcement of the Life-Sustaining Treatment (LST) Decision Act in Korea. Methods: Using the Braun and Clarke thematic analysis method, this qualitative study analyzed interview data-comprising experiences and perspectives of brain death OTD since the LST Decision Act-of 10 emergency physicians who specialized in targeted temperature management (TTM) and cared for post-cardiac arrest patients. Results: Data analysis revealed 13 subthemes and 5 themes the LST Decision Act is easier to explain to family members than brain death OTD, but it does not fit well in an emergency medical setting; many family members decide to stop LST even before physicians mention brain death or OTD; family members view stopping LST as being about comforting patients without bothering them, and decision-makers are therefore no longer willing to choose OTD; stopping LST does not always result in brain death, but cases of brain death are preceded by stopping LST; and since the LST Decision Act, the number of TTM cases and potential brain death donors has decreased. Conclusions: Unless a supplementary policy that connects stopping LST to brain death OTD is prepared, the withdrawal of LST in patients resuscitated after cardiac arrest is expected to continue, and brain death OTD is expected to decrease.
Language	English
Publishing date	2022-06-15
Publishing country	Korea (South)
Document type	Journal Article
ISSN	2671-8790
ISSN	2671-8790
DOI	10.4285/kjt.22.0005
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Article: Genetic modulation of apoptotic pathways fails to alter disease course in tripeptidyl-peptidase 1 deficient mice.

Kim, Kwi-Hye / Sleat, David E / Bernard, Ora / Lobel, Peter

Neuroscience letters

2009 Volume 453, Issue 1, Page(s) 27–30

Abstract: Late-infantile neuronal ceroid lipofuscinosis (LINCL) is a fatal, incurable neurodegenerative disease of children caused by the loss of the lysosomal protein tripeptidyl-peptidase 1 (TPP1). Previous studies have suggested that Bcl-2-dependent apoptotic ... ...

Abstract	Late-infantile neuronal ceroid lipofuscinosis (LINCL) is a fatal, incurable neurodegenerative disease of children caused by the loss of the lysosomal protein tripeptidyl-peptidase 1 (TPP1). Previous studies have suggested that Bcl-2-dependent apoptotic pathways are involved in neuronal cell death in LINCL patients and, as a result, anti-apoptotic treatments that increase Bcl-2 activity have been proposed as a potential therapeutic approach. In this study, we have directly investigated whether targeting anti-apoptotic pathways may be of value in LINCL in a mouse model of this disease that lacks TPP1 and which recapitulates many aspect of the human disease, including a greatly shortened life-span. Our approach was to genetically modify apoptotic pathways and determine the effects of these changes on the severe neurodegenerative phenotype of the LINCL mouse. LINCL mice were generated that either lacked the pro-apoptotic p53 or had increased levels of anti-apoptotic Bcl-2, changes that would exacerbate or ameliorate neuronal death, respectively, should pathways involving these proteins be important. Neither modification affected the shortened life-span of the LINCL mouse. These results suggest that either neuronal death in LINCL does not occur via apoptosis or that it occurs via apoptotic pathways not involving p53 or Bcl-2. Alternatively, pathways involving p53 and/or Bcl-2 may be involved in neuronal death under normal circumstances but may not be the only routes to this end. Importantly, our findings suggest that targeting pathways of cell death involving p53 or Bcl-2 do not represent useful directions for developing effective treatment.
MeSH term(s)	Aminopeptidases ; Animals ; Apoptosis/genetics ; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases ; Disease Models, Animal ; Endopeptidases/deficiency ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Neuronal Ceroid-Lipofuscinoses/physiopathology ; Proto-Oncogene Proteins c-bcl-2/genetics ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Serine Proteases ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism
Chemical Substances	Proto-Oncogene Proteins c-bcl-2 ; Tumor Suppressor Protein p53 ; Endopeptidases (EC 3.4.-) ; Serine Proteases (EC 3.4.-) ; Aminopeptidases (EC 3.4.11.-) ; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases (EC 3.4.14.-) ; tripeptidyl-peptidase 1 (EC 3.4.14.9)
Language	English
Publishing date	2009-02-04
Publishing country	Ireland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	194929-9
ISSN	1872-7972 ; 0304-3940
ISSN (online)	1872-7972
ISSN	0304-3940
DOI	10.1016/j.neulet.2009.01.072
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Article ; Online: Dipeptidyl-peptidase I does not functionally compensate for the loss of tripeptidyl-peptidase I in the neurodegenerative disease late-infantile neuronal ceroid lipofuscinosis.

Kim, Kwi-Hye / Pham, Christine T / Sleat, David E / Lobel, Peter

The Biochemical journal

2008 Volume 415, Issue 2, Page(s) 225–232

Abstract: LINCL (late-infantile neuronal ceroid lipofuscinosis) is a fatal neurodegenerative disease resulting from mutations in the gene encoding the lysosomal protease TPPI (tripeptidyl-peptidase I). TPPI is expressed ubiquitously throughout the body but disease ...

Abstract	LINCL (late-infantile neuronal ceroid lipofuscinosis) is a fatal neurodegenerative disease resulting from mutations in the gene encoding the lysosomal protease TPPI (tripeptidyl-peptidase I). TPPI is expressed ubiquitously throughout the body but disease appears restricted to the brain. One explanation for the absence of peripheral pathology is that in tissues other than brain, other proteases may compensate for the loss of TPPI. One such candidate is another lysosomal aminopeptidase, DPPI (dipeptidyl-peptidase I), which appears to have overlapping substrate specificity with TPPI and is expressed at relatively low levels in brain. Compensation for the loss of TPPI by DPPI may have therapeutic implications for LINCL and, in the present study, we have investigated this possibility using mouse genetic models. Our rationale was that if DPPI could compensate for the loss of TPPI in peripheral tissues, then its absence should exacerbate disease in an LINCL mouse model but, conversely, increased CNS (central nervous system) expression of DPPI should ameliorate disease. By comparing TPPI and DPPI single mutants with a double mutant lacking both proteases, we found that the loss of DPPI had no effect on accumulation of storage material, disease severity or lifespan of the LINCL mouse. Transgenic expression of DPPI resulted in a approximately 2-fold increase in DPPI activity in the brain, but this had no significant effect on survival of the LINCL mouse. These results together indicate that DPPI cannot functionally compensate for the loss of TPPI. Therapeutic approaches to increase neuronal expression of DPPI are therefore unlikely to be effective for treatment of LINCL.
MeSH term(s)	Aminopeptidases ; Animals ; Brain/metabolism ; Brain/pathology ; Cathepsin C/genetics ; Cathepsin C/metabolism ; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases ; Endopeptidases/genetics ; Endopeptidases/metabolism ; Immunohistochemistry ; Lysosomes/metabolism ; Mice ; Mice, Transgenic ; Neuronal Ceroid-Lipofuscinoses/genetics ; Neuronal Ceroid-Lipofuscinoses/metabolism ; Neuronal Ceroid-Lipofuscinoses/pathology ; Serine Proteases
Chemical Substances	Endopeptidases (EC 3.4.-) ; Serine Proteases (EC 3.4.-) ; Aminopeptidases (EC 3.4.11.-) ; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases (EC 3.4.14.-) ; Cathepsin C (EC 3.4.14.1) ; tripeptidyl-peptidase 1 (EC 3.4.14.9)
Language	English
Publishing date	2008-06-21
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2969-5
ISSN	1470-8728 ; 0006-2936 ; 0306-3275 ; 0264-6021
ISSN (online)	1470-8728
ISSN	0006-2936 ; 0306-3275 ; 0264-6021
DOI	10.1042/BJ20080411
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Article ; Online: Analysis of Factors Affecting Emergency Physicians' Attitudes toward Deceased Organ & Tissue Donation.

Lee, Dong Eun / Kim, Hyun / Park, Kwi Hwa / Park, Song Yi / Park, Seung Min / Jung, Yong Hun / Jeong, Wonjoon / Park, Kyung Hye

Journal of Korean medical science

2021 Volume 36, Issue 49, Page(s) e329

Abstract: Background: This study aimed to investigate differences in knowledge, and attitudes toward deceased organ and tissue donation of emergency physicians. Additionally, we analyzed factors affecting the attitudes toward deceased organ and tissue donation.!## ...

Abstract	Background: This study aimed to investigate differences in knowledge, and attitudes toward deceased organ and tissue donation of emergency physicians. Additionally, we analyzed factors affecting the attitudes toward deceased organ and tissue donation. Methods: We conducted a survey of specialists and residents registered with the Korean Society of Emergency Medicine in December 2020. The respondents' sex, age, position, personal registration for organ donation, experience of soliciting organ donation, participation in related education, knowledge, and attitude about brain death organ donation, and attitude toward stopping life-sustaining treatments were investigated. According to the characteristics of the respondents (specialists or residents, experience and education on organ and tissue donation), their knowledge and attitude toward deceased organ donation were compared. Stepwise hierarchical multiple regression analysis was used to investigate the factors affecting the attitudes toward deceased organ and tissue donation. Results: Of the total 428 respondents, there were 292 emergency medicine specialists and 136 medical residents. Specialists and those who registered or wished to donate organs had higher knowledge and attitude scores regarding deceased organ and tissue donation. Those who had experience recommending organ and tissue donation more than 6 times had higher knowledge scores on deceased organ and tissue donation and higher overall scores in attitude. Those who received education from the Korean Organ Donation Agency had higher knowledge scores. Specialists, and those who wished to donate or had registered as organ donors and had a higher life-sustaining treatment attitude score and knowledge about deceased organ and tissue donation, had more positive attitudes toward deceased organ and tissue donation. Conclusion: For more potential deceased organ and tissue donors to be referred for donation, there should be continuous education for emergency physicians on brain-dead organ and tissue donation-related knowledge and procedures. In addition, institutional or systematic improvements that can lead to organ donation when deciding on the withdrawal of life-sustaining treatment should be considered.
MeSH term(s)	Adult ; Attitude of Health Personnel ; Cross-Sectional Studies ; Female ; Health Knowledge, Attitudes, Practice ; Humans ; Male ; Middle Aged ; Physicians/psychology ; Surveys and Questionnaires ; Tissue and Organ Procurement
Language	English
Publishing date	2021-12-20
Publishing country	Korea (South)
Document type	Journal Article
ZDB-ID	639262-3
ISSN	1598-6357 ; 1011-8934
ISSN (online)	1598-6357
ISSN	1011-8934
DOI	10.3346/jkms.2021.36.e329
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Article: Characterization of AAV-mediated dorsal root ganglionopathy.

Buss, Nicholas / Lanigan, Lisa / Zeller, Jillynne / Cissell, Derek / Metea, Monica / Adams, Eric / Higgins, Mikayla / Kim, Kwi Hye / Budzynski, Ewa / Yang, Lin / Liu, Ye / Butt, Mark / Danos, Olivier / Fiscella, Michele

Molecular therapy. Methods & clinical development

2022 Volume 24, Page(s) 342–354

Abstract: Recent studies in non-human primates administered recombinant adeno-associated viruses (rAAVs) have shown lesions in the dorsal root ganglia (DRG) of unknown pathogenesis. In this study, rAAV9s manufactured using different purification methods alongside ... ...

Abstract	Recent studies in non-human primates administered recombinant adeno-associated viruses (rAAVs) have shown lesions in the dorsal root ganglia (DRG) of unknown pathogenesis. In this study, rAAV9s manufactured using different purification methods alongside a non-expressing Null AAV9 vector was administered to groups of cynomolgus monkeys followed by neuropathological evaluation after 4 weeks. Lesions, including neuronal degeneration, increased cellularity, and nerve fiber degeneration, were observed in the DRG, regardless of purification methods. Animals did not develop any neurological signs throughout the study, and there was no loss of function observed in neuro-electrophysiological endpoints or clear effects on intraepidermal nerve fiber density. However, magnetic resonance imaging (MRI) of animals with axonopathy showed an increase in short tau inversion recovery (STIR) intensity and decrease in fractional anisotropy. In animals administered the Null AAV9 vector, DRG lesions were not observed despite vector DNA being detected in the DRG at levels equivalent to or greater than rAAV9-treated animals. This study further supports that DRG toxicity is associated with transgene overexpression in DRGs, with particular sensitivity at the lumbar and lumbosacral level. The data from this study also showed that the nerve fiber degeneration did not correlate with any functional effect on nerve conduction but was detectable by MRI.
Language	English
Publishing date	2022-02-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2872938-9
ISSN	2329-0501 ; 2329-0501
ISSN (online)	2329-0501
ISSN	2329-0501
DOI	10.1016/j.omtm.2022.01.013
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Article ; Online: Factors associated with low trabecular bone scores in patients with end-stage kidney disease.

Yoon, Hye Eun / Kim, Yaeni / Shin, Seok Joon / Hong, Yeon Sik / Kang, Kwi Young

Journal of bone and mineral metabolism

2018 Volume 37, Issue 3, Page(s) 475–483

Abstract: The trabecular bone score (TBS) is a textural index that indirectly assesses bone trabecular microarchitecture using lumbar spine images obtained by dual-energy X-ray absorptiometry (DXA). This study compared the TBS of patients with end-stage kidney ... ...

Abstract	The trabecular bone score (TBS) is a textural index that indirectly assesses bone trabecular microarchitecture using lumbar spine images obtained by dual-energy X-ray absorptiometry (DXA). This study compared the TBS of patients with end-stage kidney disease (ESKD) with that of matched controls to identify risk factors associated with a low TBS. TBS and bone mineral density (BMD) were assessed in ESKD patients (n = 76) and age- and sex-matched control subjects (n = 76) using DXA. The TBS of both groups was then compared, and risk factors associated with a low TBS (defined as ≤ 1.31) were evaluated. The mean TBS in the ESKD group was significantly lower than that in the control group (1.34 ± 0.15 vs. 1.43 ± 0.08, respectively; p < 0.001). More subjects in the ESKD group had a low TBS [34.2% (ESRD) vs. 5.3% (controls); p < 0.001]. The TBS was negatively correlated with age, alkaline phosphatase and C-reactive protein levels, and dialysis vintage, and positively correlated with BMD at the lumbar spine, femoral neck, and hip. Multivariate analysis identified lower estimated glomerular filtration rate and increased C-reactive protein levels as being significantly associated with a low TBS. In conclusion, ESKD patients had abnormal bone microarchitecture (as assessed by the TBS). The TBS was positively correlated with BMD. Renal function and inflammatory marker levels were independently associated with a low TBS. Thus, TBS may be a useful clinical tool for assessing cancellous bone connectivity in ESKD patients.
MeSH term(s)	Adult ; Aged ; Biomarkers/metabolism ; Bone Density ; Cancellous Bone/pathology ; Female ; Humans ; Inflammation/pathology ; Kidney Failure, Chronic/complications ; Kidney Failure, Chronic/pathology ; Male ; Middle Aged ; Multivariate Analysis ; Osteoporotic Fractures/epidemiology ; Risk Factors ; Young Adult
Chemical Substances	Biomarkers
Language	English
Publishing date	2018-06-28
Publishing country	Japan
Document type	Journal Article
ZDB-ID	1295123-7
ISSN	1435-5604 ; 0914-8779
ISSN (online)	1435-5604
ISSN	0914-8779
DOI	10.1007/s00774-018-0938-8
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Article ; Online: Epigenetic Modulation of Human Induced Pluripotent Stem Cell Differentiation to Oligodendrocytes

Panagiotis Douvaras / Tomasz Rusielewicz / Kwi Hye Kim / Jeffery D. Haines / Patrizia Casaccia / Valentina Fossati

International Journal of Molecular Sciences, Vol 17, Iss 4, p

2016 Volume 614

Abstract: Pluripotent stem cells provide an invaluable tool for generating human, disease-relevant cells. Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system, characterized by myelin damage. Oligodendrocytes are the ... ...

Abstract	Pluripotent stem cells provide an invaluable tool for generating human, disease-relevant cells. Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system, characterized by myelin damage. Oligodendrocytes are the myelinating cells of the central nervous system (CNS); they differentiate from progenitor cells, and their membranes ensheath axons, providing trophic support and allowing fast conduction velocity. The current understanding of oligodendrocyte biology was founded by rodent studies, where the establishment of repressive epigenetic marks on histone proteins, followed by activation of myelin genes, leads to lineage progression. To assess whether this epigenetic regulation is conserved across species, we differentiated human embryonic and induced pluripotent stem cells to oligodendrocytes and asked whether similar histone marks and relative enzymatic activities could be detected. The transcriptional levels of enzymes responsible for methylation and acetylation of histone marks were analyzed during oligodendrocyte differentiation, and the post-translational modifications on histones were detected using immunofluorescence. These studies showed that also in human cells, differentiation along the oligodendrocyte lineage is characterized by the acquisition of multiple repressive histone marks, including deacetylation of lysine residues on histone H3 and trimethylation of residues K9 and K27. These data suggest that the epigenetic modulation of oligodendrocyte identity is highly conserved across species.
Keywords	human induced pluripotent stem cells ; oligodendrocyte differentiation ; histone modifications ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	572
Language	English
Publishing date	2016-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Residual levels of tripeptidyl-peptidase I activity dramatically ameliorate disease in late-infantile neuronal ceroid lipofuscinosis.

Sleat, David E / El-Banna, Mukarram / Sohar, Istvan / Kim, Kwi-Hye / Dobrenis, Kostantin / Walkley, Steven U / Lobel, Peter

Molecular genetics and metabolism

2008 Volume 94, Issue 2, Page(s) 222–233

Abstract: Classical late-infantile neuronal ceroid lipofuscinosis (LINCL) is a hereditary neurodegenerative disease of childhood that is caused by mutations in the gene (CLN2) encoding the lysosomal protease tripeptidyl-peptidase I (TPPI). LINCL is fatal and there ...

Abstract	Classical late-infantile neuronal ceroid lipofuscinosis (LINCL) is a hereditary neurodegenerative disease of childhood that is caused by mutations in the gene (CLN2) encoding the lysosomal protease tripeptidyl-peptidase I (TPPI). LINCL is fatal and there is no treatment of demonstrated efficacy in affected children but preclinical studies with AAV-mediated gene therapy have demonstrated promise in a mouse model. Here, we have generated mouse CLN2-mutants that express different amounts of TPPI activity to benchmark levels required for therapeutic benefits. Approximately 3% of normal TPPI activity in brain delayed disease onset and doubled lifespan to a median of approximately 9 months compared to mice expressing approximately 0.2% of normal levels. Expression of 6% of normal TPPI activity dramatically attenuated disease, with a median lifespan of approximately 20 months which approaches that of unaffected mice. While the lifespan of this hypomorph is shortened, disease is late-onset, less severe and progresses slowly compared to mice expressing lower TPPI levels. For gene therapy and other approaches that restore enzyme activity, these results suggest that 6% of normal TPPI activity throughout the CNS of affected individuals will provide a significant therapeutic benefit but higher levels will be required to cure this disease.
MeSH term(s)	Aminopeptidases ; Animals ; Brain/enzymology ; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases ; Disease Models, Animal ; Endopeptidases/analysis ; Endopeptidases/genetics ; Endopeptidases/metabolism ; Gene Targeting ; Genetic Therapy/methods ; Genetic Therapy/mortality ; Liver/enzymology ; Lysosomes/metabolism ; Mice ; Mice, Transgenic ; Mitochondrial Proton-Translocating ATPases/metabolism ; Neuronal Ceroid-Lipofuscinoses/enzymology ; Neuronal Ceroid-Lipofuscinoses/genetics ; Neuronal Ceroid-Lipofuscinoses/physiopathology ; Neuronal Ceroid-Lipofuscinoses/therapy ; Serine Proteases ; Species Specificity
Chemical Substances	Endopeptidases (EC 3.4.-) ; Serine Proteases (EC 3.4.-) ; Aminopeptidases (EC 3.4.11.-) ; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases (EC 3.4.14.-) ; tripeptidyl-peptidase 1 (EC 3.4.14.9) ; mitochondrial ATPase subunit c (EC 3.6.1.-) ; Mitochondrial Proton-Translocating ATPases (EC 3.6.3.-)
Language	English
Publishing date	2008-03-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1418518-0
ISSN	1096-7206 ; 1096-7192
ISSN (online)	1096-7206
ISSN	1096-7192
DOI	10.1016/j.ymgme.2008.01.014
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Article ; Online: Epigenetic Modulation of Human Induced Pluripotent Stem Cell Differentiation to Oligodendrocytes.

Douvaras, Panagiotis / Rusielewicz, Tomasz / Kim, Kwi Hye / Haines, Jeffery D / Casaccia, Patrizia / Fossati, Valentina

International journal of molecular sciences

2016 Volume 17, Issue 4

Abstract	Pluripotent stem cells provide an invaluable tool for generating human, disease-relevant cells. Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system, characterized by myelin damage. Oligodendrocytes are the myelinating cells of the central nervous system (CNS); they differentiate from progenitor cells, and their membranes ensheath axons, providing trophic support and allowing fast conduction velocity. The current understanding of oligodendrocyte biology was founded by rodent studies, where the establishment of repressive epigenetic marks on histone proteins, followed by activation of myelin genes, leads to lineage progression. To assess whether this epigenetic regulation is conserved across species, we differentiated human embryonic and induced pluripotent stem cells to oligodendrocytes and asked whether similar histone marks and relative enzymatic activities could be detected. The transcriptional levels of enzymes responsible for methylation and acetylation of histone marks were analyzed during oligodendrocyte differentiation, and the post-translational modifications on histones were detected using immunofluorescence. These studies showed that also in human cells, differentiation along the oligodendrocyte lineage is characterized by the acquisition of multiple repressive histone marks, including deacetylation of lysine residues on histone H3 and trimethylation of residues K9 and K27. These data suggest that the epigenetic modulation of oligodendrocyte identity is highly conserved across species.
MeSH term(s)	Acetylation ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Cell Differentiation/genetics ; Cells, Cultured ; Epigenesis, Genetic ; Histones/metabolism ; Humans ; Induced Pluripotent Stem Cells/cytology ; Induced Pluripotent Stem Cells/metabolism ; Microscopy, Fluorescence ; Nerve Tissue Proteins/metabolism ; Oligodendrocyte Transcription Factor 2 ; Oligodendroglia/cytology ; Oligodendroglia/metabolism ; PAX6 Transcription Factor/metabolism ; Protein Processing, Post-Translational
Chemical Substances	Basic Helix-Loop-Helix Transcription Factors ; Histones ; Nerve Tissue Proteins ; OLIG2 protein, human ; Oligodendrocyte Transcription Factor 2 ; PAX6 Transcription Factor
Language	English
Publishing date	2016-04-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms17040614
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In stock of ZB MED Cologne/Königswinter

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Order via subito