umu.sePublications
Change search
Link to record
Permanent link

Direct link
BETA
Jones, Iwan
Publications (8 of 8) Show all publications
Jones, I., Yelhekar, T. D., Wiberg, R., Kingham, P. J., Johansson, S., Wiberg, M. & Carlsson, L. (2018). Development and validation of an in vitro model system to study peripheral sensory neuron development and injury. Scientific Reports, 8, Article ID 15961.
Open this publication in new window or tab >>Development and validation of an in vitro model system to study peripheral sensory neuron development and injury
Show others...
2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 15961Article in journal (Refereed) Published
Abstract [en]

The ability to discriminate between diverse types of sensation is mediated by heterogeneous populations of peripheral sensory neurons. Human peripheral sensory neurons are inaccessible for research and efforts to study their development and disease have been hampered by the availability of relevant model systems. The in vitro differentiation of peripheral sensory neurons from human embryonic stem cells therefore provides an attractive alternative since an unlimited source of biological material can be generated for studies that specifically address development and injury. The work presented in this study describes the derivation of peripheral sensory neurons from human embryonic stem cells using small molecule inhibitors. The differentiated neurons express canonical- and modality-specific peripheral sensory neuron markers with subsets exhibiting functional properties of human nociceptive neurons that include tetrodotoxin-resistant sodium currents and repetitive action potentials. Moreover, the derived cells associate with human donor Schwann cells and can be used as a model system to investigate the molecular mechanisms underlying neuronal death following peripheral nerve injury. The quick and efficient derivation of genetically diverse peripheral sensory neurons from human embryonic stem cells offers unlimited access to these specialised cell types and provides an invaluable in vitro model system for future studies.

Place, publisher, year, edition, pages
Nature Publishing Group, 2018
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-153701 (URN)10.1038/s41598-018-34280-3 (DOI)000448589200037 ()30374154 (PubMedID)
Funder
Swedish Research Council, 22292Gunvor och Josef Anérs stiftelseVästerbotten County Council
Available from: 2018-12-05 Created: 2018-12-05 Last updated: 2018-12-05Bibliographically approved
Jones, I., Novikova, L. N., Novikov, L. N., Renardy, M., Ullrich, A., Wiberg, M., . . . Kingham, P. J. (2018). Regenerative effects of human embryonic stem cell-derived neural crest cells for treatment of peripheral nerve injury. Journal of Tissue Engineering and Regenerative Medicine, 12(4), E2099-E2109
Open this publication in new window or tab >>Regenerative effects of human embryonic stem cell-derived neural crest cells for treatment of peripheral nerve injury
Show others...
2018 (English)In: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, E-ISSN 1932-7005, Vol. 12, no 4, p. E2099-E2109Article in journal (Refereed) Published
Abstract [en]

Surgical intervention is the current gold standard treatment following peripheral nerve injury. However, this approach has limitations, and full recovery of both motor and sensory modalities often remains incomplete. The development of artificial nerve grafts that either complement or replace current surgical procedures is therefore of paramount importance. An essential component of artificial grafts is biodegradable conduits and transplanted cells that provide trophic support during the regenerative process. Neural crest cells are promising support cell candidates because they are the parent population to many peripheral nervous system lineages. In this study, neural crest cells were differentiated from human embryonic stem cells. The differentiated cells exhibited typical stellate morphology and protein expression signatures that were comparable with native neural crest. Conditioned media harvested from the differentiated cells contained a range of biologically active trophic factors and was able to stimulate in vitro neurite outgrowth. Differentiated neural crest cells were seeded into a biodegradable nerve conduit, and their regeneration potential was assessed in a rat sciatic nerve injury model. A robust regeneration front was observed across the entire width of the conduit seeded with the differentiated neural crest cells. Moreover, the up-regulation of several regeneration-related genes was observed within the dorsal root ganglion and spinal cord segments harvested from transplanted animals. Our results demonstrate that the differentiated neural crest cells are biologically active and provide trophic support to stimulate peripheral nerve regeneration. Differentiated neural crest cells are therefore promising supporting cell candidates to aid in peripheral nerve repair.

Keywords
artificial nerve graft, human embryonic stem cells, neural crest cells, peripheral nerve injuries, ripheral nervous system, VELOPMENTAL EVOLUTION, V314B, P95 e Gabsang, 2007, NATURE BIOTECHNOLOGY, V25, P1468
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-147466 (URN)10.1002/term.2642 (DOI)000430395400024 ()29327452 (PubMedID)
Funder
Swedish Research Council, 2014-2306
Available from: 2018-05-28 Created: 2018-05-28 Last updated: 2018-06-09Bibliographically approved
Hagglund, A.-C., Jones, I. & Carlsson, L. (2017). A novel mouse model of anterior segment dysgenesis (ASD): conditional deletion of Tsc1 disrupts ciliary body and iris development. Disease Models and Mechanisms, 10(3), 245-257
Open this publication in new window or tab >>A novel mouse model of anterior segment dysgenesis (ASD): conditional deletion of Tsc1 disrupts ciliary body and iris development
2017 (English)In: Disease Models and Mechanisms, ISSN 1754-8403, E-ISSN 1754-8411, Vol. 10, no 3, p. 245-257Article in journal (Refereed) Published
Abstract [en]

Development of the cornea, lens, ciliary body and iris within the anterior segment of the eye involves coordinated interaction between cells originating from the ciliary margin of the optic cup, the overlying periocular mesenchyme and the lens epithelium. Anterior segment dysgenesis (ASD) encompasses a spectrum of developmental syndromes that affect these anterior segment tissues. ASD conditions arise as a result of dominantly inherited genetic mutations and result in both ocular-specific and systemic forms of dysgenesis that are best exemplified by aniridia and Axenfeld-Rieger syndrome, respectively. Extensive clinical overlap in disease presentation amongst ASD syndromes creates challenges for correct diagnosis and classification. The use of animal models has therefore proved to be a robust approach for unravelling this complex genotypic and phenotypic heterogeneity. However, despite these successes, it is clear that additional genes that underlie several ASD syndromes remain unidentified. Here, we report the characterisation of a novel mouse model of ASD. Conditional deletion of Tsc1 during eye development leads to a premature upregulation of mTORC1 activity within the ciliary margin, periocular mesenchyme and lens epithelium. This aberrant mTORC1 signalling within the ciliary margin in particular leads to a reduction in the number of cells that express Pax6, Bmp4 and Msx1. Sustained mTORC1 signalling also induces a decrease in ciliary margin progenitor cell proliferation and a consequent failure of ciliary body and iris development in postnatal animals. Our study therefore identifies Tsc1 as a novel candidate ASD gene. Furthermore, the Tsc1-ablated mouse model also provides a valuable resource for future studies concerning the molecular mechanisms underlying ASD and acts as a platform for evaluating therapeutic approaches for the treatment of visual disorders.

Keywords
Tsc1, mTORC1, Pax6, Ciliary body, Iris, Anterior segment dysgenesis
National Category
Medical Genetics
Identifiers
urn:nbn:se:umu:diva-133816 (URN)10.1242/dmm.028605 (DOI)000395717100005 ()28250050 (PubMedID)
Available from: 2017-04-18 Created: 2017-04-18 Last updated: 2018-06-09Bibliographically approved
Jones, I., Hägglund, A.-C., Törnqvist, G., Nord, C., Ahlgren, U. & Carlsson, L. (2015). A novel mouse model of tuberous sclerosis complex (TSC): eye-specific Tsc1-ablation disrupts visual-pathway development. Disease Models and Mechanisms, 8(12), 1517-1529
Open this publication in new window or tab >>A novel mouse model of tuberous sclerosis complex (TSC): eye-specific Tsc1-ablation disrupts visual-pathway development
Show others...
2015 (English)In: Disease Models and Mechanisms, ISSN 1754-8403, E-ISSN 1754-8411, Vol. 8, no 12, p. 1517-1529Article in journal (Refereed) Published
Abstract [en]

Tuberous sclerosis complex (TSC) is an autosomal dominant syndrome that is best characterised by neurodevelopmental deficits and the presence of benign tumours (called hamartomas) in affected organs. This multi-organ disorder results from inactivating point mutations in either the TSC1 or the TSC2 genes and consequent activation of the canonical mammalian target of rapamycin complex 1 signalling (mTORC1) pathway. Because lesions to the eye are central to TSC diagnosis, we report here the generation and characterisation of the first eye-specific TSC mouse model. We demonstrate that conditional ablation of Tsc1 in eye-committed progenitor cells leads to the accelerated differentiation and subsequent ectopic radial migration of retinal ganglion cells. This results in an increase in retinal ganglion cell apoptosis and consequent regionalised axonal loss within the optic nerve and topographical changes to the contra- and ipsilateral input within the dorsal lateral geniculate nucleus. Eyes from adult mice exhibit aberrant retinal architecture and display all the classic neuropathological hallmarks of TSC, including an increase in organ and cell size, ring heterotopias, hamartomas with retinal detachment, and lamination defects. Our results provide the first major insight into the molecular etiology of TSC within the developing eye and demonstrate a pivotal role for Tsc1 in regulating various aspects of visual-pathway development. Our novel mouse model therefore provides a valuable resource for future studies concerning the molecular mechanisms underlying TSC and also as a platform to evaluate new therapeutic approaches for the treatment of this multi-organ disorder.

National Category
Other Basic Medicine
Identifiers
urn:nbn:se:umu:diva-120197 (URN)10.1242/dmm.021972 (DOI)000368905300004 ()26449264 (PubMedID)
Available from: 2016-05-11 Created: 2016-05-11 Last updated: 2018-06-07Bibliographically approved
Svenningsson, A., Dring, A. M., Fogdell-Hahn, A., Jones, I., Engdahl, E., Lundkvist, M., . . . Gilthorpe, J. D. (2013). Fatal neuroinflammation in a case of multiple sclerosis with anti-natalizumab antibodies. Neurology, 80(10), 965-967
Open this publication in new window or tab >>Fatal neuroinflammation in a case of multiple sclerosis with anti-natalizumab antibodies
Show others...
2013 (English)In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 80, no 10, p. 965-967Article in journal, Editorial material (Other academic) Published
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-67965 (URN)10.1212/WNL.0b013e3182840be3 (DOI)000315773500022 ()
Available from: 2013-04-11 Created: 2013-04-09 Last updated: 2018-06-08Bibliographically approved
von Hofsten, J., Karlsson, J., Jones, I. & Olsson, P.-E. (2002). Expression and Regulation of Fushi Tarazu Factor-1 and Steroidogenic Genes During Reproduction in Arctic Char (Salvelinus alpinus). Biology of Reproduction, 67(4), 1297-1304
Open this publication in new window or tab >>Expression and Regulation of Fushi Tarazu Factor-1 and Steroidogenic Genes During Reproduction in Arctic Char (Salvelinus alpinus)
2002 (English)In: Biology of Reproduction, ISSN 0006-3363, E-ISSN 1529-7268, Vol. 67, no 4, p. 1297-1304Article in journal (Refereed) Published
Abstract [en]

Teleost fushi tarazu factor-1 (FTZ-F1) is a potential regulator of steroidogenesis. The present study shows sex-specific regulation of Arctic char fushi tarazu factor-1 (acFF1) and steroidogenic genes during reproductive maturation and in response to hormone treatment. A link between gonadal expression of acFF1, steroidogenic acute regulatory protein (StAR), and cytochrome P450-11A (CYP11A), was observed in the reproductive maturation process, as elevated acFF1 mRNA and protein levels preceded increased StAR and CYP11A transcription. Sex-specific differences were observed as estrogen treatment resulted in down-regulated levels of acFF1 mRNA in testis and male head kidney, whereas no significant effect was observed in females. 11-Ketotestosterone (11-KT) down-regulated CYP11A and 3beta-hydroxysteroid dehydrogenase (3betaHSD) in head kidney and up-regulated CYP11A in testis. StAR remained unaffected by hormone treatment. This suggests that acFF1 is controlled by 17beta-estradiol, whereas the effects on CYP11A and 3betaHSD are mediated by 11-KT. Coexpression of acFF1, StAR, and CYP11A was observed in head kidney, in addition to gonads, indicating correlation between these steroidogenic genes. StAR and acFF1 were also coexpressed in liver, suggesting a potential role in cholesterol metabolism. Although these results indicate conserved steroidogenic functions for FTZ-F1 among vertebrates, they also raise the question of additional roles for FTZ-F1 in teleosts.

Place, publisher, year, edition, pages
Society for the Study of Reproduction, 2002
Keywords
gene regulation, seasonal reproduction, steroid hormones
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-4279 (URN)10.1095/biolreprod.102.005181 (DOI)000178266200033 ()12297548 (PubMedID)
Available from: 2004-11-19 Created: 2004-11-19 Last updated: 2019-01-22Bibliographically approved
von Hofsten, J., Jones, I., Karlsson, J. & Olsson, P.-E. (2001). Developmental expression patterns of FTZ-F1 homologues in zebrafish (Danio rerio). General and Comparative Endocrinology, 121(2), 146-155
Open this publication in new window or tab >>Developmental expression patterns of FTZ-F1 homologues in zebrafish (Danio rerio)
2001 (English)In: General and Comparative Endocrinology, ISSN 0016-6480, E-ISSN 1095-6840, Vol. 121, no 2, p. 146-155Article in journal (Refereed) Published
Abstract [en]

The fushi tarazu factor 1 (FTZ-F1) gene family constitutes a subgroup of orphan nuclear receptors which can be divided into two groups (LRH/FTF- and SF-1/Ad4BP-like) based on sequence homology, function, and tissue distribution. Analysis of zebrafish FTZ-F1 homologues (zFF1 and ff1b) during embryogenesis indicated distinct expression patterns for both genes. Besides the previously observed expression in pituitary/hypothalamus and mandibular arch, zFF1 transcripts were also detected in domains corresponding to the pronephric duct, somites, liver, and hindbrain. Additionally, ff1b transcripts were detected at other developmental stages than earlier documented. Comparative sequence analysis showed that zFF1 exhibited higher sequence similarity to the LRH/FTF group than the SF-1/Ad4BP group, whereas ff1b was indistinguishable between the groups. These observations, coupled with obtained expression patterns, indicate that zebrafish FTZ-F1 homologues exhibit characteristics that are indicative of both LRH/FTF- and SF-1/Ad4BP-like genes.

Place, publisher, year, edition, pages
Academic Press, 2001
Keywords
FTZ-F1, zFF1, zFF1Am, zFF1B, ff1b, zebrafish, embryogenesis, pituitary, pronephric duct, urogenital ridge, mandibular arch, hindbrain, liver, Danio rerio
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-4278 (URN)10.1006/gcen.2000.7582 (DOI)000167271700003 ()11178880 (PubMedID)
Available from: 2004-11-19 Created: 2004-11-19 Last updated: 2019-01-22Bibliographically approved
Muthukrishnan, U., Natarajan, B., Mäger, I., Levén May, H., Jones, I., Corso, G., . . . Gilthorpe, J. D.The exosome membrane localization of histones is independent of DNA and upregulated in response to stress.
Open this publication in new window or tab >>The exosome membrane localization of histones is independent of DNA and upregulated in response to stress
Show others...
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Extracellular histones contribute to many acute and chronic diseases but also populate the secretomes of healthy cells and biofluids. However, a secretory pathway for histones has not been described. Here we report that core and linker histones localize to multivesicular bodies and are secreted via exosomes. Histones are tightly associated with the exosome membrane, with N-terminal domains exposed, in a DNA-independent manner. Furthermore, rapid upregulation of exosomal histones occurs following heat stress, accompanied by enhanced vesicle secretion and a shift towards a population of smaller vesicles. Proteomic analyses identified the downregulation of endosomal sorting complex required for transport (ESCRT) complex as a possible mechanism underlying increased histone secretion.We show for the first time that membrane-associated histones are actively secreted from intact cells via the multivesicular body/exosomal pathway. We demonstrate a novel pathway for extracellular histone release that may have a role in both health and disease.

Keywords
Extracellular histones, extracellular vesicles, exosomes, exoDNA, cellular stress, ESCRT complex, proteomics
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-147419 (URN)
Available from: 2018-05-03 Created: 2018-05-03 Last updated: 2018-06-09
Organisations

Search in DiVA

Show all publications