---
_id: '14639'
abstract:
- lang: eng
text: "Background: Biallelic variants in OGDHL, encoding part of the α-ketoglutarate
dehydrogenase complex, have been associated with highly heterogeneous neurological
and neurodevelopmental disorders. However, the validity of this association remains
to be confirmed. A second OGDHL patient cohort was recruited to carefully assess
the gene-disease relationship.\r\nMethods: Using an unbiased genotype-first approach,
we screened large, multiethnic aggregated sequencing datasets worldwide for biallelic
OGDHL variants. We used CRISPR/Cas9 to generate zebrafish knockouts of ogdhl,
ogdh paralogs, and dhtkd1 to investigate functional relationships and impact during
development. Functional complementation with patient variant transcripts was conducted
to systematically assess protein functionality as a readout for pathogenicity.\r\nResults:
A cohort of 14 individuals from 12 unrelated families exhibited highly variable
clinical phenotypes, with the majority of them presenting at least one additional
variant, potentially accounting for a blended phenotype and complicating phenotypic
understanding. We also uncovered extreme clinical heterogeneity and high allele
frequencies, occasionally incompatible with a fully penetrant recessive disorder.
Human cDNA of previously described and new variants were tested in an ogdhl zebrafish
knockout model, adding functional evidence for variant reclassification. We disclosed
evidence of hypomorphic alleles as well as a loss-of-function variant without
deleterious effects in zebrafish variant testing also showing discordant familial
segregation, challenging the relationship of OGDHL as a conventional Mendelian
gene. Going further, we uncovered evidence for a complex compensatory relationship
among OGDH, OGDHL, and DHTKD1 isoenzymes that are associated with neurodevelopmental
disorders and exhibit complex transcriptional compensation patterns with partial
functional redundancy.\r\nConclusions: Based on the results of genetic, clinical,
and functional studies, we formed three hypotheses in which to frame observations:
biallelic OGDHL variants lead to a highly variable monogenic disorder, variants
in OGDHL are following a complex pattern of inheritance, or they may not be causative
at all. Our study further highlights the continuing challenges of assessing the
validity of reported disease-gene associations and effects of variants identified
in these genes. This is particularly more complicated in making genetic diagnoses
based on identification of variants in genes presenting a highly heterogenous
phenotype such as “OGDHL-related disorders”."
article_number: '102'
article_processing_charge: Yes
article_type: original
author:
- first_name: Sheng-Jia
full_name: Lin, Sheng-Jia
last_name: Lin
- first_name: Barbara
full_name: Vona, Barbara
last_name: Vona
- first_name: Tracy
full_name: Lau, Tracy
last_name: Lau
- first_name: Kevin
full_name: Huang, Kevin
id: 3b3d2888-1ff6-11ee-9fa6-8f209ca91fe3
last_name: Huang
orcid: 0000-0002-2512-7812
- first_name: Maha S.
full_name: Zaki, Maha S.
last_name: Zaki
- first_name: Huda Shujaa
full_name: Aldeen, Huda Shujaa
last_name: Aldeen
- first_name: Ehsan Ghayoor
full_name: Karimiani, Ehsan Ghayoor
last_name: Karimiani
- first_name: Clarissa
full_name: Rocca, Clarissa
last_name: Rocca
- first_name: Mahmoud M.
full_name: Noureldeen, Mahmoud M.
last_name: Noureldeen
- first_name: Ahmed K.
full_name: Saad, Ahmed K.
last_name: Saad
- first_name: Cassidy
full_name: Petree, Cassidy
last_name: Petree
- first_name: Tobias
full_name: Bartolomaeus, Tobias
last_name: Bartolomaeus
- first_name: Rami
full_name: Abou Jamra, Rami
last_name: Abou Jamra
- first_name: Giovanni
full_name: Zifarelli, Giovanni
last_name: Zifarelli
- first_name: Aditi
full_name: Gotkhindikar, Aditi
last_name: Gotkhindikar
- first_name: Ingrid M.
full_name: Wentzensen, Ingrid M.
last_name: Wentzensen
- first_name: Mingjuan
full_name: Liao, Mingjuan
last_name: Liao
- first_name: Emalyn Elise
full_name: Cork, Emalyn Elise
last_name: Cork
- first_name: Pratishtha
full_name: Varshney, Pratishtha
last_name: Varshney
- first_name: Narges
full_name: Hashemi, Narges
last_name: Hashemi
- first_name: Mohammad Hasan
full_name: Mohammadi, Mohammad Hasan
last_name: Mohammadi
- first_name: Aboulfazl
full_name: Rad, Aboulfazl
last_name: Rad
- first_name: Juanita
full_name: Neira, Juanita
last_name: Neira
- first_name: Mehran Beiraghi
full_name: Toosi, Mehran Beiraghi
last_name: Toosi
- first_name: Cordula
full_name: Knopp, Cordula
last_name: Knopp
- first_name: Ingo
full_name: Kurth, Ingo
last_name: Kurth
- first_name: Thomas D.
full_name: Challman, Thomas D.
last_name: Challman
- first_name: Rebecca
full_name: Smith, Rebecca
last_name: Smith
- first_name: Asmahan
full_name: Abdalla, Asmahan
last_name: Abdalla
- first_name: Thomas
full_name: Haaf, Thomas
last_name: Haaf
- first_name: Mohnish
full_name: Suri, Mohnish
last_name: Suri
- first_name: Manali
full_name: Joshi, Manali
last_name: Joshi
- first_name: Wendy K.
full_name: Chung, Wendy K.
last_name: Chung
- first_name: Andres
full_name: Moreno-De-Luca, Andres
last_name: Moreno-De-Luca
- first_name: Henry
full_name: Houlden, Henry
last_name: Houlden
- first_name: Reza
full_name: Maroofian, Reza
last_name: Maroofian
- first_name: Gaurav K.
full_name: Varshney, Gaurav K.
last_name: Varshney
citation:
ama: Lin S-J, Vona B, Lau T, et al. Evaluating the association of biallelic OGDHL
variants with significant phenotypic heterogeneity. Genome Medicine. 2023;15.
doi:10.1186/s13073-023-01258-4
apa: Lin, S.-J., Vona, B., Lau, T., Huang, K., Zaki, M. S., Aldeen, H. S., … Varshney,
G. K. (2023). Evaluating the association of biallelic OGDHL variants with significant
phenotypic heterogeneity. Genome Medicine. Springer Nature. https://doi.org/10.1186/s13073-023-01258-4
chicago: Lin, Sheng-Jia, Barbara Vona, Tracy Lau, Kevin Huang, Maha S. Zaki, Huda
Shujaa Aldeen, Ehsan Ghayoor Karimiani, et al. “Evaluating the Association of
Biallelic OGDHL Variants with Significant Phenotypic Heterogeneity.” Genome
Medicine. Springer Nature, 2023. https://doi.org/10.1186/s13073-023-01258-4.
ieee: S.-J. Lin et al., “Evaluating the association of biallelic OGDHL variants
with significant phenotypic heterogeneity,” Genome Medicine, vol. 15. Springer
Nature, 2023.
ista: Lin S-J, Vona B, Lau T, Huang K, Zaki MS, Aldeen HS, Karimiani EG, Rocca C,
Noureldeen MM, Saad AK, Petree C, Bartolomaeus T, Abou Jamra R, Zifarelli G, Gotkhindikar
A, Wentzensen IM, Liao M, Cork EE, Varshney P, Hashemi N, Mohammadi MH, Rad A,
Neira J, Toosi MB, Knopp C, Kurth I, Challman TD, Smith R, Abdalla A, Haaf T,
Suri M, Joshi M, Chung WK, Moreno-De-Luca A, Houlden H, Maroofian R, Varshney
GK. 2023. Evaluating the association of biallelic OGDHL variants with significant
phenotypic heterogeneity. Genome Medicine. 15, 102.
mla: Lin, Sheng-Jia, et al. “Evaluating the Association of Biallelic OGDHL Variants
with Significant Phenotypic Heterogeneity.” Genome Medicine, vol. 15, 102,
Springer Nature, 2023, doi:10.1186/s13073-023-01258-4.
short: S.-J. Lin, B. Vona, T. Lau, K. Huang, M.S. Zaki, H.S. Aldeen, E.G. Karimiani,
C. Rocca, M.M. Noureldeen, A.K. Saad, C. Petree, T. Bartolomaeus, R. Abou Jamra,
G. Zifarelli, A. Gotkhindikar, I.M. Wentzensen, M. Liao, E.E. Cork, P. Varshney,
N. Hashemi, M.H. Mohammadi, A. Rad, J. Neira, M.B. Toosi, C. Knopp, I. Kurth,
T.D. Challman, R. Smith, A. Abdalla, T. Haaf, M. Suri, M. Joshi, W.K. Chung, A.
Moreno-De-Luca, H. Houlden, R. Maroofian, G.K. Varshney, Genome Medicine 15 (2023).
date_created: 2023-12-04T08:10:55Z
date_published: 2023-11-23T00:00:00Z
date_updated: 2023-12-04T08:17:22Z
day: '23'
ddc:
- '570'
doi: 10.1186/s13073-023-01258-4
extern: '1'
file:
- access_level: open_access
checksum: 279efd212005549aba817a487d56d363
content_type: application/pdf
creator: dernst
date_created: 2023-12-04T08:15:43Z
date_updated: 2023-12-04T08:15:43Z
file_id: '14640'
file_name: 2023_GenomeMed_Lin.pdf
file_size: 14791081
relation: main_file
success: 1
file_date_updated: 2023-12-04T08:15:43Z
has_accepted_license: '1'
intvolume: ' 15'
keyword:
- Genetics (clinical)
- Genetics
- Molecular Biology
- Molecular Medicine
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '11'
oa: 1
oa_version: Published Version
publication: Genome Medicine
publication_identifier:
issn:
- 1756-994X
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
status: public
title: Evaluating the association of biallelic OGDHL variants with significant phenotypic
heterogeneity
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 15
year: '2023'
...
---
_id: '9018'
abstract:
- lang: eng
text: Anti-silencing function 1 (ASF1) is a conserved H3-H4 histone chaperone involved
in histone dynamics during replication, transcription, and DNA repair. Overexpressed
in proliferating tissues including many tumors, ASF1 has emerged as a promising
therapeutic target. Here, we combine structural, computational, and biochemical
approaches to design peptides that inhibit the ASF1-histone interaction. Starting
from the structure of the human ASF1-histone complex, we developed a rational
design strategy combining epitope tethering and optimization of interface contacts
to identify a potent peptide inhibitor with a dissociation constant of 3 nM. When
introduced into cultured cells, the inhibitors impair cell proliferation, perturb
cell-cycle progression, and reduce cell migration and invasion in a manner commensurate
with their affinity for ASF1. Finally, we find that direct injection of the most
potent ASF1 peptide inhibitor in mouse allografts reduces tumor growth. Our results
open new avenues to use ASF1 inhibitors as promising leads for cancer therapy.
article_processing_charge: No
article_type: original
author:
- first_name: May M
full_name: Bakail, May M
id: FB3C3F8E-522F-11EA-B186-22963DDC885E
last_name: Bakail
orcid: 0000-0002-9592-1587
- first_name: Albane
full_name: Gaubert, Albane
last_name: Gaubert
- first_name: Jessica
full_name: Andreani, Jessica
last_name: Andreani
- first_name: Gwenaëlle
full_name: Moal, Gwenaëlle
last_name: Moal
- first_name: Guillaume
full_name: Pinna, Guillaume
last_name: Pinna
- first_name: Ekaterina
full_name: Boyarchuk, Ekaterina
last_name: Boyarchuk
- first_name: Marie-Cécile
full_name: Gaillard, Marie-Cécile
last_name: Gaillard
- first_name: Regis
full_name: Courbeyrette, Regis
last_name: Courbeyrette
- first_name: Carl
full_name: Mann, Carl
last_name: Mann
- first_name: Jean-Yves
full_name: Thuret, Jean-Yves
last_name: Thuret
- first_name: Bérengère
full_name: Guichard, Bérengère
last_name: Guichard
- first_name: Brice
full_name: Murciano, Brice
last_name: Murciano
- first_name: Nicolas
full_name: Richet, Nicolas
last_name: Richet
- first_name: Adeline
full_name: Poitou, Adeline
last_name: Poitou
- first_name: Claire
full_name: Frederic, Claire
last_name: Frederic
- first_name: Marie-Hélène
full_name: Le Du, Marie-Hélène
last_name: Le Du
- first_name: Morgane
full_name: Agez, Morgane
last_name: Agez
- first_name: Caroline
full_name: Roelants, Caroline
last_name: Roelants
- first_name: Zachary A.
full_name: Gurard-Levin, Zachary A.
last_name: Gurard-Levin
- first_name: Geneviève
full_name: Almouzni, Geneviève
last_name: Almouzni
- first_name: Nadia
full_name: Cherradi, Nadia
last_name: Cherradi
- first_name: Raphael
full_name: Guerois, Raphael
last_name: Guerois
- first_name: Françoise
full_name: Ochsenbein, Françoise
last_name: Ochsenbein
citation:
ama: Bakail MM, Gaubert A, Andreani J, et al. Design on a rational basis of high-affinity
peptides inhibiting the histone chaperone ASF1. Cell Chemical Biology.
2019;26(11):1573-1585.e10. doi:10.1016/j.chembiol.2019.09.002
apa: Bakail, M. M., Gaubert, A., Andreani, J., Moal, G., Pinna, G., Boyarchuk, E.,
… Ochsenbein, F. (2019). Design on a rational basis of high-affinity peptides
inhibiting the histone chaperone ASF1. Cell Chemical Biology. Elsevier.
https://doi.org/10.1016/j.chembiol.2019.09.002
chicago: Bakail, May M, Albane Gaubert, Jessica Andreani, Gwenaëlle Moal, Guillaume
Pinna, Ekaterina Boyarchuk, Marie-Cécile Gaillard, et al. “Design on a Rational
Basis of High-Affinity Peptides Inhibiting the Histone Chaperone ASF1.” Cell
Chemical Biology. Elsevier, 2019. https://doi.org/10.1016/j.chembiol.2019.09.002.
ieee: M. M. Bakail et al., “Design on a rational basis of high-affinity peptides
inhibiting the histone chaperone ASF1,” Cell Chemical Biology, vol. 26,
no. 11. Elsevier, p. 1573–1585.e10, 2019.
ista: Bakail MM, Gaubert A, Andreani J, Moal G, Pinna G, Boyarchuk E, Gaillard M-C,
Courbeyrette R, Mann C, Thuret J-Y, Guichard B, Murciano B, Richet N, Poitou A,
Frederic C, Le Du M-H, Agez M, Roelants C, Gurard-Levin ZA, Almouzni G, Cherradi
N, Guerois R, Ochsenbein F. 2019. Design on a rational basis of high-affinity
peptides inhibiting the histone chaperone ASF1. Cell Chemical Biology. 26(11),
1573–1585.e10.
mla: Bakail, May M., et al. “Design on a Rational Basis of High-Affinity Peptides
Inhibiting the Histone Chaperone ASF1.” Cell Chemical Biology, vol. 26,
no. 11, Elsevier, 2019, p. 1573–1585.e10, doi:10.1016/j.chembiol.2019.09.002.
short: M.M. Bakail, A. Gaubert, J. Andreani, G. Moal, G. Pinna, E. Boyarchuk, M.-C.
Gaillard, R. Courbeyrette, C. Mann, J.-Y. Thuret, B. Guichard, B. Murciano, N.
Richet, A. Poitou, C. Frederic, M.-H. Le Du, M. Agez, C. Roelants, Z.A. Gurard-Levin,
G. Almouzni, N. Cherradi, R. Guerois, F. Ochsenbein, Cell Chemical Biology 26
(2019) 1573–1585.e10.
date_created: 2021-01-19T11:04:50Z
date_published: 2019-11-21T00:00:00Z
date_updated: 2023-02-23T13:46:53Z
day: '21'
doi: 10.1016/j.chembiol.2019.09.002
extern: '1'
external_id:
pmid:
- '31543461'
intvolume: ' 26'
issue: '11'
keyword:
- Clinical Biochemistry
- Molecular Medicine
- Biochemistry
- Molecular Biology
- Pharmacology
- Drug Discovery
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1016/j.chembiol.2019.09.002
month: '11'
oa: 1
oa_version: Published Version
page: 1573-1585.e10
pmid: 1
publication: Cell Chemical Biology
publication_identifier:
issn:
- 2451-9456
publication_status: published
publisher: Elsevier
quality_controlled: '1'
status: public
title: Design on a rational basis of high-affinity peptides inhibiting the histone
chaperone ASF1
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 26
year: '2019'
...
---
_id: '8439'
abstract:
- lang: eng
text: Lipopolysaccharides (LPS) are complex glycolipids forming the outside layer
of Gram-negative bacteria. Their hydrophobic and heterogeneous nature greatly
hampers their structural study in an environment similar to the bacterial surface.
We have studied LPS purified from E. coli and pathogenic P. aeruginosa with long
O-antigen polysaccharides assembled in solution as vesicles or elongated micelles.
Solid-state NMR with magic-angle spinning permitted the identification of NMR
signals arising from regions with different flexibilities in the LPS, from the
lipid components to the O-antigen polysaccharides. Atomic scale data on the LPS
enabled the study of the interaction of gentamicin antibiotic bound to P. aeruginosa
LPS, for which we could confirm that a specific oligosaccharide is involved in
the antibiotic binding. The possibility to study LPS alone and bound to a ligand
when it is assembled in membrane-like structures opens great prospects for the
investigation of proteins and antibiotics that specifically target such an important
molecule at the surface of Gram-negative bacteria.
article_processing_charge: No
article_type: original
author:
- first_name: Cedric
full_name: Laguri, Cedric
last_name: Laguri
- first_name: Alba
full_name: Silipo, Alba
last_name: Silipo
- first_name: Alessandra M.
full_name: Martorana, Alessandra M.
last_name: Martorana
- first_name: Paul
full_name: Schanda, Paul
id: 7B541462-FAF6-11E9-A490-E8DFE5697425
last_name: Schanda
orcid: 0000-0002-9350-7606
- first_name: Roberta
full_name: Marchetti, Roberta
last_name: Marchetti
- first_name: Alessandra
full_name: Polissi, Alessandra
last_name: Polissi
- first_name: Antonio
full_name: Molinaro, Antonio
last_name: Molinaro
- first_name: Jean-Pierre
full_name: Simorre, Jean-Pierre
last_name: Simorre
citation:
ama: Laguri C, Silipo A, Martorana AM, et al. Solid state NMR studies of intact
lipopolysaccharide endotoxin. ACS Chemical Biology. 2018;13(8):2106-2113.
doi:10.1021/acschembio.8b00271
apa: Laguri, C., Silipo, A., Martorana, A. M., Schanda, P., Marchetti, R., Polissi,
A., … Simorre, J.-P. (2018). Solid state NMR studies of intact lipopolysaccharide
endotoxin. ACS Chemical Biology. American Chemical Society. https://doi.org/10.1021/acschembio.8b00271
chicago: Laguri, Cedric, Alba Silipo, Alessandra M. Martorana, Paul Schanda, Roberta
Marchetti, Alessandra Polissi, Antonio Molinaro, and Jean-Pierre Simorre. “Solid
State NMR Studies of Intact Lipopolysaccharide Endotoxin.” ACS Chemical Biology.
American Chemical Society, 2018. https://doi.org/10.1021/acschembio.8b00271.
ieee: C. Laguri et al., “Solid state NMR studies of intact lipopolysaccharide
endotoxin,” ACS Chemical Biology, vol. 13, no. 8. American Chemical Society,
pp. 2106–2113, 2018.
ista: Laguri C, Silipo A, Martorana AM, Schanda P, Marchetti R, Polissi A, Molinaro
A, Simorre J-P. 2018. Solid state NMR studies of intact lipopolysaccharide endotoxin.
ACS Chemical Biology. 13(8), 2106–2113.
mla: Laguri, Cedric, et al. “Solid State NMR Studies of Intact Lipopolysaccharide
Endotoxin.” ACS Chemical Biology, vol. 13, no. 8, American Chemical Society,
2018, pp. 2106–13, doi:10.1021/acschembio.8b00271.
short: C. Laguri, A. Silipo, A.M. Martorana, P. Schanda, R. Marchetti, A. Polissi,
A. Molinaro, J.-P. Simorre, ACS Chemical Biology 13 (2018) 2106–2113.
date_created: 2020-09-18T10:05:09Z
date_published: 2018-07-02T00:00:00Z
date_updated: 2021-01-12T08:19:16Z
day: '02'
doi: 10.1021/acschembio.8b00271
extern: '1'
intvolume: ' 13'
issue: '8'
keyword:
- Molecular Medicine
- Biochemistry
- General Medicine
language:
- iso: eng
month: '07'
oa_version: None
page: 2106-2113
publication: ACS Chemical Biology
publication_identifier:
issn:
- 1554-8929
- 1554-8937
publication_status: published
publisher: American Chemical Society
quality_controlled: '1'
status: public
title: Solid state NMR studies of intact lipopolysaccharide endotoxin
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 13
year: '2018'
...
---
_id: '11067'
abstract:
- lang: eng
text: Neural progenitor cells (NeuPCs) possess a unique nuclear architecture that
changes during differentiation. Nucleoporins are linked with cell-type-specific
gene regulation, coupling physical changes in nuclear structure to transcriptional
output; but, whether and how they coordinate with key fate-determining transcription
factors is unclear. Here we show that the nucleoporin Nup153 interacts with Sox2
in adult NeuPCs, where it is indispensable for their maintenance and controls
neuronal differentiation. Genome-wide analyses show that Nup153 and Sox2 bind
and co-regulate hundreds of genes. Binding of Nup153 to gene promoters or transcriptional
end sites correlates with increased or decreased gene expression, respectively,
and inhibiting Nup153 expression alters open chromatin configurations at its target
genes, disrupts genomic localization of Sox2, and promotes differentiation in
vitro and a gliogenic fate switch in vivo. Together, these findings reveal that
nuclear structural proteins may exert bimodal transcriptional effects to control
cell fate.
article_processing_charge: No
article_type: original
author:
- first_name: Tomohisa
full_name: Toda, Tomohisa
last_name: Toda
- first_name: Jonathan Y.
full_name: Hsu, Jonathan Y.
last_name: Hsu
- first_name: Sara B.
full_name: Linker, Sara B.
last_name: Linker
- first_name: Lauren
full_name: Hu, Lauren
last_name: Hu
- first_name: Simon T.
full_name: Schafer, Simon T.
last_name: Schafer
- first_name: Jerome
full_name: Mertens, Jerome
last_name: Mertens
- first_name: Filipe V.
full_name: Jacinto, Filipe V.
last_name: Jacinto
- first_name: Martin W
full_name: HETZER, Martin W
id: 86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed
last_name: HETZER
orcid: 0000-0002-2111-992X
- first_name: Fred H.
full_name: Gage, Fred H.
last_name: Gage
citation:
ama: Toda T, Hsu JY, Linker SB, et al. Nup153 interacts with Sox2 to enable bimodal
gene regulation and maintenance of neural progenitor cells. Cell Stem Cell.
2017;21(5):618-634.e7. doi:10.1016/j.stem.2017.08.012
apa: Toda, T., Hsu, J. Y., Linker, S. B., Hu, L., Schafer, S. T., Mertens, J., …
Gage, F. H. (2017). Nup153 interacts with Sox2 to enable bimodal gene regulation
and maintenance of neural progenitor cells. Cell Stem Cell. Elsevier. https://doi.org/10.1016/j.stem.2017.08.012
chicago: Toda, Tomohisa, Jonathan Y. Hsu, Sara B. Linker, Lauren Hu, Simon T. Schafer,
Jerome Mertens, Filipe V. Jacinto, Martin Hetzer, and Fred H. Gage. “Nup153 Interacts
with Sox2 to Enable Bimodal Gene Regulation and Maintenance of Neural Progenitor
Cells.” Cell Stem Cell. Elsevier, 2017. https://doi.org/10.1016/j.stem.2017.08.012.
ieee: T. Toda et al., “Nup153 interacts with Sox2 to enable bimodal gene
regulation and maintenance of neural progenitor cells,” Cell Stem Cell,
vol. 21, no. 5. Elsevier, p. 618–634.e7, 2017.
ista: Toda T, Hsu JY, Linker SB, Hu L, Schafer ST, Mertens J, Jacinto FV, Hetzer
M, Gage FH. 2017. Nup153 interacts with Sox2 to enable bimodal gene regulation
and maintenance of neural progenitor cells. Cell Stem Cell. 21(5), 618–634.e7.
mla: Toda, Tomohisa, et al. “Nup153 Interacts with Sox2 to Enable Bimodal Gene Regulation
and Maintenance of Neural Progenitor Cells.” Cell Stem Cell, vol. 21, no.
5, Elsevier, 2017, p. 618–634.e7, doi:10.1016/j.stem.2017.08.012.
short: T. Toda, J.Y. Hsu, S.B. Linker, L. Hu, S.T. Schafer, J. Mertens, F.V. Jacinto,
M. Hetzer, F.H. Gage, Cell Stem Cell 21 (2017) 618–634.e7.
date_created: 2022-04-07T07:46:12Z
date_published: 2017-11-02T00:00:00Z
date_updated: 2022-07-18T08:33:07Z
day: '02'
doi: 10.1016/j.stem.2017.08.012
extern: '1'
external_id:
pmid:
- '28919367'
intvolume: ' 21'
issue: '5'
keyword:
- Cell Biology
- Genetics
- Molecular Medicine
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1016/j.stem.2017.08.012
month: '11'
oa: 1
oa_version: Published Version
page: 618-634.e7
pmid: 1
publication: Cell Stem Cell
publication_identifier:
issn:
- 1934-5909
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Nup153 interacts with Sox2 to enable bimodal gene regulation and maintenance
of neural progenitor cells
type: journal_article
user_id: 72615eeb-f1f3-11ec-aa25-d4573ddc34fd
volume: 21
year: '2017'
...
---
_id: '11079'
abstract:
- lang: eng
text: Aging is a major risk factor for many human diseases, and in vitro generation
of human neurons is an attractive approach for modeling aging-related brain disorders.
However, modeling aging in differentiated human neurons has proved challenging.
We generated neurons from human donors across a broad range of ages, either by
iPSC-based reprogramming and differentiation or by direct conversion into induced
neurons (iNs). While iPSCs and derived neurons did not retain aging-associated
gene signatures, iNs displayed age-specific transcriptional profiles and revealed
age-associated decreases in the nuclear transport receptor RanBP17. We detected
an age-dependent loss of nucleocytoplasmic compartmentalization (NCC) in donor
fibroblasts and corresponding iNs and found that reduced RanBP17 impaired NCC
in young cells, while iPSC rejuvenation restored NCC in aged cells. These results
show that iNs retain important aging-related signatures, thus allowing modeling
of the aging process in vitro, and they identify impaired NCC as an important
factor in human aging.
article_processing_charge: No
article_type: original
author:
- first_name: Jerome
full_name: Mertens, Jerome
last_name: Mertens
- first_name: Apuã C.M.
full_name: Paquola, Apuã C.M.
last_name: Paquola
- first_name: Manching
full_name: Ku, Manching
last_name: Ku
- first_name: Emily
full_name: Hatch, Emily
last_name: Hatch
- first_name: Lena
full_name: Böhnke, Lena
last_name: Böhnke
- first_name: Shauheen
full_name: Ladjevardi, Shauheen
last_name: Ladjevardi
- first_name: Sean
full_name: McGrath, Sean
last_name: McGrath
- first_name: Benjamin
full_name: Campbell, Benjamin
last_name: Campbell
- first_name: Hyungjun
full_name: Lee, Hyungjun
last_name: Lee
- first_name: Joseph R.
full_name: Herdy, Joseph R.
last_name: Herdy
- first_name: J. Tiago
full_name: Gonçalves, J. Tiago
last_name: Gonçalves
- first_name: Tomohisa
full_name: Toda, Tomohisa
last_name: Toda
- first_name: Yongsung
full_name: Kim, Yongsung
last_name: Kim
- first_name: Jürgen
full_name: Winkler, Jürgen
last_name: Winkler
- first_name: Jun
full_name: Yao, Jun
last_name: Yao
- first_name: Martin W
full_name: HETZER, Martin W
id: 86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed
last_name: HETZER
orcid: 0000-0002-2111-992X
- first_name: Fred H.
full_name: Gage, Fred H.
last_name: Gage
citation:
ama: Mertens J, Paquola ACM, Ku M, et al. Directly reprogrammed human neurons retain
aging-associated transcriptomic signatures and reveal age-related nucleocytoplasmic
defects. Cell Stem Cell. 2015;17(6):705-718. doi:10.1016/j.stem.2015.09.001
apa: Mertens, J., Paquola, A. C. M., Ku, M., Hatch, E., Böhnke, L., Ladjevardi,
S., … Gage, F. H. (2015). Directly reprogrammed human neurons retain aging-associated
transcriptomic signatures and reveal age-related nucleocytoplasmic defects. Cell
Stem Cell. Elsevier. https://doi.org/10.1016/j.stem.2015.09.001
chicago: Mertens, Jerome, Apuã C.M. Paquola, Manching Ku, Emily Hatch, Lena Böhnke,
Shauheen Ladjevardi, Sean McGrath, et al. “Directly Reprogrammed Human Neurons
Retain Aging-Associated Transcriptomic Signatures and Reveal Age-Related Nucleocytoplasmic
Defects.” Cell Stem Cell. Elsevier, 2015. https://doi.org/10.1016/j.stem.2015.09.001.
ieee: J. Mertens et al., “Directly reprogrammed human neurons retain aging-associated
transcriptomic signatures and reveal age-related nucleocytoplasmic defects,” Cell
Stem Cell, vol. 17, no. 6. Elsevier, pp. 705–718, 2015.
ista: Mertens J, Paquola ACM, Ku M, Hatch E, Böhnke L, Ladjevardi S, McGrath S,
Campbell B, Lee H, Herdy JR, Gonçalves JT, Toda T, Kim Y, Winkler J, Yao J, Hetzer
M, Gage FH. 2015. Directly reprogrammed human neurons retain aging-associated
transcriptomic signatures and reveal age-related nucleocytoplasmic defects. Cell
Stem Cell. 17(6), 705–718.
mla: Mertens, Jerome, et al. “Directly Reprogrammed Human Neurons Retain Aging-Associated
Transcriptomic Signatures and Reveal Age-Related Nucleocytoplasmic Defects.” Cell
Stem Cell, vol. 17, no. 6, Elsevier, 2015, pp. 705–18, doi:10.1016/j.stem.2015.09.001.
short: J. Mertens, A.C.M. Paquola, M. Ku, E. Hatch, L. Böhnke, S. Ladjevardi, S.
McGrath, B. Campbell, H. Lee, J.R. Herdy, J.T. Gonçalves, T. Toda, Y. Kim, J.
Winkler, J. Yao, M. Hetzer, F.H. Gage, Cell Stem Cell 17 (2015) 705–718.
date_created: 2022-04-07T07:49:51Z
date_published: 2015-12-03T00:00:00Z
date_updated: 2022-07-18T08:44:21Z
day: '03'
doi: 10.1016/j.stem.2015.09.001
extern: '1'
external_id:
pmid:
- '26456686'
intvolume: ' 17'
issue: '6'
keyword:
- Cell Biology
- Genetics
- Molecular Medicine
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1016/j.stem.2015.09.001
month: '12'
oa: 1
oa_version: Published Version
page: 705-718
pmid: 1
publication: Cell Stem Cell
publication_identifier:
issn:
- 1934-5909
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Directly reprogrammed human neurons retain aging-associated transcriptomic
signatures and reveal age-related nucleocytoplasmic defects
type: journal_article
user_id: 72615eeb-f1f3-11ec-aa25-d4573ddc34fd
volume: 17
year: '2015'
...
---
_id: '11117'
abstract:
- lang: eng
text: Over the last years it has become evident that the nuclear envelope (NE) is
more than a passive membrane barrier that separates the nucleus from the cytoplasm.
The NE not only controls the trafficking of macromolecules between the nucleoplasm
and the cytosol, but also provides anchoring sites for chromosomes and cytoskeleton
to the nuclear periphery. Targeting of chromatin to the NE might actually be part
of gene expression regulation in eukaryotes. Mutations in certain NE proteins
are associated with a diversity of human diseases, including muscular dystrophy,
neuropathy, lipodistrophy, torsion dystonia and the premature aging condition
progeria. Despite the importance of the NE for cell division and differentiation,
relatively little is known about its biogenesis and its role in human diseases.
It is our goal to provide a comprehensive view of the NE and to discuss possible
implications of NE-associated changes for gene expression, chromatin organization
and signal transduction.
article_processing_charge: No
article_type: review
author:
- first_name: M. A.
full_name: D’Angelo, M. A.
last_name: D’Angelo
- first_name: Martin W
full_name: HETZER, Martin W
id: 86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed
last_name: HETZER
orcid: 0000-0002-2111-992X
citation:
ama: D’Angelo MA, Hetzer M. The role of the nuclear envelope in cellular organization.
Cellular and Molecular Life Sciences. 2006;63(3):316-332. doi:10.1007/s00018-005-5361-3
apa: D’Angelo, M. A., & Hetzer, M. (2006). The role of the nuclear envelope
in cellular organization. Cellular and Molecular Life Sciences. Springer
Nature. https://doi.org/10.1007/s00018-005-5361-3
chicago: D’Angelo, M. A., and Martin Hetzer. “The Role of the Nuclear Envelope in
Cellular Organization.” Cellular and Molecular Life Sciences. Springer
Nature, 2006. https://doi.org/10.1007/s00018-005-5361-3.
ieee: M. A. D’Angelo and M. Hetzer, “The role of the nuclear envelope in cellular
organization,” Cellular and Molecular Life Sciences, vol. 63, no. 3. Springer
Nature, pp. 316–332, 2006.
ista: D’Angelo MA, Hetzer M. 2006. The role of the nuclear envelope in cellular
organization. Cellular and Molecular Life Sciences. 63(3), 316–332.
mla: D’Angelo, M. A., and Martin Hetzer. “The Role of the Nuclear Envelope in Cellular
Organization.” Cellular and Molecular Life Sciences, vol. 63, no. 3, Springer
Nature, 2006, pp. 316–32, doi:10.1007/s00018-005-5361-3.
short: M.A. D’Angelo, M. Hetzer, Cellular and Molecular Life Sciences 63 (2006)
316–332.
date_created: 2022-04-07T07:56:22Z
date_published: 2006-01-02T00:00:00Z
date_updated: 2022-07-18T08:56:58Z
day: '02'
doi: 10.1007/s00018-005-5361-3
extern: '1'
external_id:
pmid:
- '16389459'
intvolume: ' 63'
issue: '3'
keyword:
- Cell Biology
- Cellular and Molecular Neuroscience
- Pharmacology
- Molecular Biology
- Molecular Medicine
language:
- iso: eng
month: '01'
oa_version: None
page: 316-332
pmid: 1
publication: Cellular and Molecular Life Sciences
publication_identifier:
eissn:
- 1420-9071
issn:
- 1420-682X
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: The role of the nuclear envelope in cellular organization
type: journal_article
user_id: 72615eeb-f1f3-11ec-aa25-d4573ddc34fd
volume: 63
year: '2006'
...