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Patthey, Cedric
Alternative names
Publications (10 of 21) Show all publications
Papadogiannis, V., Hockman, D., Mercurio, S., Ramsay, C., Hintze, M., Patthey, C., . . . Shimeld, S. M. (2023). Evolution of the expression and regulation of the nuclear hormone receptor ERR gene family in the chordate lineage. Developmental Biology, 504, 12-24
Open this publication in new window or tab >>Evolution of the expression and regulation of the nuclear hormone receptor ERR gene family in the chordate lineage
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2023 (English)In: Developmental Biology, ISSN 0012-1606, E-ISSN 1095-564X, Vol. 504, p. 12-24Article in journal (Refereed) Published
Abstract [en]

The Estrogen Related Receptor (ERR) nuclear hormone receptor genes have a wide diversity of roles in vertebrate development. In embryos, ERR genes are expressed in several tissues, including the central and peripheral nervous systems. Here we seek to establish the evolutionary history of chordate ERR genes, their expression and their regulation. We examine ERR expression in mollusc, amphioxus and sea squirt embryos, finding the single ERR orthologue is expressed in the nervous system in all three, with muscle expression also found in the two chordates. We show that most jawed vertebrates and lampreys have four ERR paralogues, and that vertebrate ERR genes were ancestrally linked to Estrogen Receptor genes. One of the lamprey paralogues shares conserved expression domains with jawed vertebrate ERRγ in the embryonic vestibuloacoustic ganglion, eye, brain and spinal cord. Hypothesising that conserved expression derives from conserved regulation, we identify a suite of pan-vertebrate conserved non-coding sequences in ERR introns. We use transgenesis in lamprey and chicken embryos to show that these sequences are regulatory and drive reporter gene expression in the nervous system. Our data suggest an ancient association between ERR and the nervous system, including expression in cells associated with photosensation and mechanosensation. This includes the origin in the vertebrate common ancestor of a suite of regulatory elements in the 3’ introns that drove nervous system expression and have been conserved from this point onwards.

National Category
Developmental Biology
Identifiers
urn:nbn:se:umu:diva-214682 (URN)10.1016/j.ydbio.2023.09.003 (DOI)37696353 (PubMedID)2-s2.0-85171360049 (Scopus ID)
Available from: 2023-09-28 Created: 2023-09-28 Last updated: 2023-09-28Bibliographically approved
Lidström, T., Cumming, J., Gaur, R., Frängsmyr, L., Pateras, I., Mickert, M. J., . . . Öhlund, D. (2023). Extracellular galectin 4 drives immune evasion and promotes T-cell apoptosis in pancreatic cancer. Cancer immunology research, 11(1), 72-92
Open this publication in new window or tab >>Extracellular galectin 4 drives immune evasion and promotes T-cell apoptosis in pancreatic cancer
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2023 (English)In: Cancer immunology research, ISSN 2326-6066, Vol. 11, no 1, p. 72-92Article in journal (Refereed) Published
Abstract [en]

Pancreatic ductal adenocarcinoma (PDAC) is characterized by rich deposits of extracellular matrix (ECM), affecting the pathophysiology of the disease. Here, we identified galectin 4 (gal 4) as a cancer cell produced protein deposited into the ECM of PDAC tumors and detected high circulating levels of gal 4 in PDAC patients. In orthotopic transplantation experiments we observed increased infiltration of T-cells and prolonged survival in immunocompetent mice transplanted with cancer cells with reduced expression of gal 4. Increased survival was not observed in immunodeficient RAG1-/- mice, demonstrating that the effect was mediated by the adaptive immune system. Furthermore, by performing single-cell RNA-sequencing we found that the myeloid compartment and cancer-associated fibroblast (CAF) subtypes were altered in the transplanted tumors. Reduced gal 4 expression was associated with higher proportion of myofibroblastic CAFs and reduced numbers of inflammatory CAFs. We also found higher proportions of M1 macrophages, T-cells and antigen presenting dendritic cells in tumors with reduced gal 4 expression. Using a co-culture system, we observed that extracellular gal 4 induced apoptosis in T-cells by binding N-glycosylation residues on CD3 epsilon/delta. Hence, we show that gal 4 is involved in immune evasion and identify gal 4 as a promising drug target for overcoming immunosuppression in PDAC. 

Place, publisher, year, edition, pages
American Association for Cancer Research, 2023
Keywords
Galectin 4, pancreatic cancer, immunosuppression, extracellular matrix, drug target
National Category
Cancer and Oncology
Research subject
Immunology; Medicine; Oncology
Identifiers
urn:nbn:se:umu:diva-201042 (URN)10.1158/2326-6066.CIR-21-1088 (DOI)36478037 (PubMedID)2-s2.0-85145492684 (Scopus ID)
Funder
The Swedish Foundation for International Cooperation in Research and Higher Education (STINT), PT2015-6432Swedish Cancer Society, AMP17-877, LP18-2202, LP20-2257, LP 21-2298Swedish Research Council, 2017-01531The Kempe Foundations, JCK-1301, SMK-1765Swedish Society of Medicine, SLS-890521, SLS-786661, SLS-691681, SLS-591551Västerbotten County Council, RV-930167, VLL-643451, VLL-832001Sjöberg FoundationKnut and Alice Wallenberg FoundationMarianne and Marcus Wallenberg Foundation, MMW 2020.0189Swedish Cancer Society, CAN 2017/332, CAN 2017/827, 20 1339 PjFSwedish Cancer Society, AMP-18-919Knut and Alice Wallenberg Foundation
Note

Originally included in thesis in manuscript form. 

Available from: 2022-11-16 Created: 2022-11-16 Last updated: 2023-10-18Bibliographically approved
Papadogiannis, V., Pennati, A., Parker, H. J., Rothbächer, U., Patthey, C., Bronner, M. E. & Shimeld, S. M. (2022). Hmx gene conservation identifies the origin of vertebrate cranial ganglia. Nature, 605(7911), 701-705
Open this publication in new window or tab >>Hmx gene conservation identifies the origin of vertebrate cranial ganglia
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2022 (English)In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 605, no 7911, p. 701-705Article in journal (Refereed) Published
Abstract [en]

The evolutionary origin of vertebrates included innovations in sensory processing associated with the acquisition of a predatory lifestyle1. Vertebrates perceive external stimuli through sensory systems serviced by cranial sensory ganglia, whose neurons arise predominantly from cranial placodes; however, the understanding of the evolutionary origin of placodes and cranial sensory ganglia is hampered by the anatomical differences between living lineages and the difficulty in assigning homology between cell types and structures. Here we show that the homeobox transcription factor Hmx is a constitutive component of vertebrate sensory ganglion development and that in the tunicate Ciona intestinalis, Hmx is necessary and sufficient to drive the differentiation programme of bipolar tail neurons, cells previously thought to be homologues of neural crest2,3. Using Ciona and lamprey transgenesis, we demonstrate that a unique, tandemly duplicated enhancer pair regulated Hmx expression in the stem-vertebrate lineage. We also show notably robust vertebrate Hmx enhancer function in Ciona, demonstrating that deep conservation of the upstream regulatory network spans the evolutionary origin of vertebrates. These experiments demonstrate regulatory and functional conservation between Ciona and vertebrate Hmx, and point to bipolar tail neurons as homologues of cranial sensory ganglia.

Place, publisher, year, edition, pages
Springer Nature, 2022
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-196110 (URN)10.1038/s41586-022-04742-w (DOI)000797332400002 ()35585239 (PubMedID)2-s2.0-85130232006 (Scopus ID)
Available from: 2022-06-17 Created: 2022-06-17 Last updated: 2022-06-17Bibliographically approved
Lara-Ramirez, R., Perez-Gonzalez, C., Anselmi, C., Patthey, C. & Shimeld, S. M. (2019). A Notch-regulated proliferative stem cell zone in the developing spinal cord is an ancestral vertebrate trait. Development, 146(1), Article ID dev166595.
Open this publication in new window or tab >>A Notch-regulated proliferative stem cell zone in the developing spinal cord is an ancestral vertebrate trait
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2019 (English)In: Development, ISSN 0950-1991, E-ISSN 1477-9129, Vol. 146, no 1, article id dev166595Article in journal (Refereed) Published
Abstract [en]

Vertebrates have evolved the most sophisticated nervous systems we know. These differ from the nervous systems of invertebrates in several ways, including the evolution of new cell types, and the emergence and elaboration of patterning mechanisms to organise cells in time and space. Vertebrates also generally have many more cells in their central nervous systems than invertebrates, and an increase in neural cell number may have contributed to the sophisticated anatomy of the brain and spinal cord. Here, we study how increased cell number evolved in the vertebrate central nervous system, investigating the regulation of cell proliferation in the lamprey spinal cord. Markers of proliferation show that a ventricular progenitor zone is found throughout the lamprey spinal cord. We show that inhibition of Notch signalling disrupts the maintenance of this zone. When Notch is blocked, progenitor cells differentiate precociously, the proliferative ventricular zone is lost and differentiation markers become expressed throughout the spinal cord. Comparison with other chordates suggests that the emergence of a persistent Notch-regulated proliferative progenitor zone was a crucial step for the evolution of vertebrate spinal cord complexity.

Place, publisher, year, edition, pages
Company of Biologists, 2019
Keywords
Lamprey, Notch signalling, Evolution, Proliferation, PCNA, Coe, Spinal cord
National Category
Developmental Biology
Identifiers
urn:nbn:se:umu:diva-155973 (URN)10.1242/dev.166595 (DOI)000455850900002 ()30552127 (PubMedID)2-s2.0-85059796751 (Scopus ID)
Available from: 2019-02-07 Created: 2019-02-07 Last updated: 2021-09-16Bibliographically approved
Panaliappan, T. K., Slekiene, L., Gunhaga, L. & Patthey, C. (2019). Extensive apoptosis during the formation of the terminal nerve ganglion by olfactory placode-derived cells with distinct molecular markers. Differentiation, 110, 8-16
Open this publication in new window or tab >>Extensive apoptosis during the formation of the terminal nerve ganglion by olfactory placode-derived cells with distinct molecular markers
2019 (English)In: Differentiation, ISSN 0301-4681, E-ISSN 1432-0436, Vol. 110, p. 8-16Article in journal (Refereed) Published
Abstract [en]

The terminal nerve ganglion (TNG) is a well-known structure of the peripheral nervous system in cartilaginous and teleost fishes. It derives from the olfactory placode during embryonic development. While the differentiation and migration of gonadotropin releasing hormone (GnRH)-expressing neurons from the olfactory placode has been well documented, the TNG has been neglected in birds and mammals, and its development is less well described. Here we describe the formation of a ganglion-like structure from migratory olfactory placodal cells in chicken. The TNG is surrounded by neural crest cells, but in contrast to other cranial sensory ganglia, we observed no neural crest corridor, and olfactory unsheathing cells appear only after the onset of neuronal migration. We identified Isl1 and Lhx2 as two transcription factors that label neuronal subpopulations in the forming TNG, distinct from GnRH1(+) cells, thereby revealing a diversity of cell types during the formation of the TNG. We also provide evidence for extensive apoptosis in the terminal nerve ganglion shortly after its formation, but not in other cranial sensory ganglia. Moreover, at later stages placode-derived neurons expressing GnRH1, Isl1 and/or Lhx2 become incorporated in the telencephalon. The integration of TNG neurons into the telencephalon together with the earlier widespread apoptosis in the TNG might be an explanation why the TNG in mammals and birds is much smaller compared to other vertebrates.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Terminal nerve ganglion, Apoptosis, Lhx2, GnRH, Isl1, Chicken
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-167041 (URN)10.1016/j.diff.2019.09.003 (DOI)000498845100002 ()31539705 (PubMedID)2-s2.0-85072197946 (Scopus ID)
Funder
Swedish Research Council, 2017-01430_3
Available from: 2020-01-08 Created: 2020-01-08 Last updated: 2023-03-24Bibliographically approved
Signoret, C., Ng, E., Da Silva, S., Tack, A., Voss, U., Lidö, H. H., . . . Balachandran, C. (2019). Well-being of early-career researchers: insights from a Swedish survey. Higher Education Policy, 32(2), 273-296
Open this publication in new window or tab >>Well-being of early-career researchers: insights from a Swedish survey
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2019 (English)In: Higher Education Policy, ISSN 0952-8733, E-ISSN 1740-3863, Vol. 32, no 2, p. 273-296Article in journal (Refereed) Published
Abstract [en]

Several studies have documented the importance of optimal work situation and the general well-being of early-career researchers (ECRs) for enhancing the academic performance of universities. Yet, most studies focused on specific categories of ECRs, or on specific academic disciplines as well as on specific outcomes. With this study, we recognize the need for a broader sample encompassing different categories of ECRs across academic disciplines. In a national survey of Swedish universities, the National Junior Faculty of Sweden (NJF) collected data from ECRs in order to study the influence of work situation and well-being on perceived scientific environment. We observed that work situation and well-being are interdependent and jointly influence each other in shaping the conditions for ideal scientific environment. Importantly, we employ structural equation model (SEM) analysis to account for the endogenous relationship between work situation and personal well-being in predicting perceived scientific environment. Results from SEM indicate that support from the university, work time management, job clarity, contract length and quality of life satisfaction were related to the perceived possibility of conducting the best science. Our research also highlighted individual differences across demographic factors and contract length in the perceived work situation and the possibility of conducting the best science.

Place, publisher, year, edition, pages
Springer, 2019
Keywords
early-career researchers, survey, academia, well-being, work situation, Sweden
National Category
Learning
Research subject
education
Identifiers
urn:nbn:se:umu:diva-144739 (URN)10.1057/s41307-018-0080-1 (DOI)000468989500007 ()2-s2.0-85041856311 (Scopus ID)
Available from: 2018-02-12 Created: 2018-02-12 Last updated: 2023-03-23Bibliographically approved
Panaliappan, T. K., Wittmann, W., Jidigam, V. K., Mercurio, S., Bertolini, J. A., Sghari, S., . . . Gunhaga, L. (2018). Sox2 is required for olfactory pit formation and olfactory neurogenesis through BMP restriction and Hes5 upregulation. Development, 145(2), Article ID dev153791.
Open this publication in new window or tab >>Sox2 is required for olfactory pit formation and olfactory neurogenesis through BMP restriction and Hes5 upregulation
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2018 (English)In: Development, ISSN 0950-1991, E-ISSN 1477-9129, Vol. 145, no 2, article id dev153791Article in journal (Refereed) Published
Abstract [en]

The transcription factor Sox2 is necessary to maintain pluripotency of embryonic stem cells, and to regulate neural development. Neurogenesis in the vertebrate olfactory epithelium persists from embryonic stages through adulthood. The role Sox2 plays for the development of the olfactory epithelium and neurogenesis within has, however, not been determined. Here, by analysing Sox2 conditional knockout mouse embryos and chick embryos deprived of Sox2 in the olfactory epithelium using CRISPR-Cas9, we show that Sox2 activity is crucial for the induction of the neural progenitor gene Hes5 and for subsequent differentiation of the neuronal lineage. Our results also suggest that Sox2 activity promotes the neurogenic domain in the nasal epithelium by restricting Bmp4 expression. The Sox2-deficient olfactory epithelium displays diminished cell cycle progression and proliferation, a dramatic increase in apoptosis and finally olfactory pit atrophy. Moreover, chromatin immunoprecipitation data show that Sox2 directly binds to the Hes5 promoter in both the PNS and CNS. Taken together, our results indicate that Sox2 is essential to establish, maintain and expand the neuronal progenitor pool by suppressing Bmp4 and upregulating Hes5 expression.

Place, publisher, year, edition, pages
Company of Biologists Ltd, 2018
Keywords
Sox2, Hes5, Olfactory epithelium, Neurogenesis, Mouse
National Category
Developmental Biology Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-145166 (URN)10.1242/dev.153791 (DOI)000424412000009 ()2-s2.0-85041301091 (Scopus ID)
Available from: 2018-02-23 Created: 2018-02-23 Last updated: 2023-03-24Bibliographically approved
Patthey, C., Tong, Y. G., Tait, C. M. & Wilson, S. I. (2017). Evolution of the functionally conserved DCC gene in birds. Scientific Reports, 7, Article ID 42029.
Open this publication in new window or tab >>Evolution of the functionally conserved DCC gene in birds
2017 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 7, article id 42029Article in journal (Refereed) Published
Abstract [en]

Understanding the loss of conserved genes is critical for determining how phenotypic diversity is generated. Here we focus on the evolution of DCC, a gene that encodes a highly conserved neural guidance receptor. Disruption of DCC in animal models and humans results in major neurodevelopmental defects including commissural axon defects. Here we examine DCC evolution in birds, which is of particular interest as a major model system in neurodevelopmental research. We found the DCC containing locus was disrupted several times during evolution, resulting in both gene losses and faster evolution rate of salvaged genes. These data suggest that DCC had been lost independently twice during bird evolution, including in chicken and zebra finch, whereas it was preserved in many other closely related bird species, including ducks. Strikingly, we observed that commissural axon trajectory appeared similar regardless of whether DCC could be detected or not. We conclude that the DCC locus is susceptible to genomic instability leading to independent disruptions in different branches of birds and a significant influence on evolution rate. Overall, the phenomenon of loss or molecular evolution of a highly conserved gene without apparent phenotype change is of conceptual importance for understanding molecular evolution of key biological processes.

Place, publisher, year, edition, pages
Macmillan Publishers Ltd., 2017
Keywords
embryology, evolutionary developmental biology, neuronal development
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-131968 (URN)10.1038/srep42029 (DOI)000394782700001 ()2-s2.0-85014088301 (Scopus ID)
Available from: 2017-02-27 Created: 2017-02-27 Last updated: 2023-03-23Bibliographically approved
Lara-Ramirez, R., Poncelet, G., Patthey, C. & Shimeld, S. M. (2017). The structure, splicing, synteny and expression of lamprey COE genes and the evolution of the COE gene family in chordates. Development, Genes and Evolution, 227(5), 319-338
Open this publication in new window or tab >>The structure, splicing, synteny and expression of lamprey COE genes and the evolution of the COE gene family in chordates
2017 (English)In: Development, Genes and Evolution, ISSN 0949-944X, E-ISSN 1432-041X, Vol. 227, no 5, p. 319-338Article in journal (Refereed) Published
Abstract [en]

COE genes encode transcription factors that have been found in all metazoans examined to date. They possess a distinctive domain structure that includes a DNA-binding domain (DBD), an IPT/TIG domain and a helix-loop-helix (HLH) domain. An intriguing feature of the COE HLH domain is that in jawed vertebrates it is composed of three helices, compared to two in invertebrates. We report the isolation and expression of two COE genes from the brook lamprey Lampetra planeri and compare these to COE genes from the lampreys Lethenteron japonicum and Petromyzon marinus. Molecular phylogenetic analyses do not resolve the relationship of lamprey COE genes to jawed vertebrate paralogues, though synteny mapping shows that they all derive from duplication of a common ancestral genomic region. All lamprey genes encode conserved DBD, IPT/TIG and HLH domains; however, the HLH domain of lamprey COE-A genes encodes only two helices while COE-B encodes three helices. We also identified COE-B splice variants encoding either two or three helices in the HLH domain, along with other COE-A and COE-B splice variants affecting the DBD and C-terminal transactivation regions. In situ hybridisation revealed expression in the lamprey nervous system including the brain, spinal cord and cranial sensory ganglia. We also detected expression of both genes in mesenchyme in the pharyngeal arches and underlying the notochord. This allows us to establish the primitive vertebrate expression pattern for COE genes and compare this to that of invertebrate chordates and other animals to develop a model for COE gene evolution in chordates.

Place, publisher, year, edition, pages
SPRINGER, 2017
Keywords
COE, Ebf, Neurogenesis, Lamprey, Cranial ganglia, Pharyngeal arch, Brain
National Category
Developmental Biology
Identifiers
urn:nbn:se:umu:diva-140049 (URN)10.1007/s00427-017-0591-6 (DOI)000410737300003 ()2-s2.0-85028891148 (Scopus ID)
Available from: 2017-10-03 Created: 2017-10-03 Last updated: 2023-03-24Bibliographically approved
Patthey, C., Clifford, H., Haerty, W., Ponting, C. P., Shimeld, S. M. & Begbie, J. (2016). Identification of molecular signatures specific for distinct cranial sensory ganglia in the developing chick. Neural Development, 11, Article ID 3.
Open this publication in new window or tab >>Identification of molecular signatures specific for distinct cranial sensory ganglia in the developing chick
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2016 (English)In: Neural Development, ISSN 1749-8104, Vol. 11, article id 3Article in journal (Refereed) Published
Abstract [en]

Background: The cranial sensory ganglia represent populations of neurons with distinct functions, or sensory modalities. The production of individual ganglia from distinct neurogenic placodes with different developmental pathways provides a powerful model to investigate the acquisition of specific sensory modalities. To date there is a limited range of gene markers available to examine the molecular pathways underlying this process.

Results: Transcriptional profiles were generated for populations of differentiated neurons purified from distinct cranial sensory ganglia using microdissection in embryonic chicken followed by FAC-sorting and RNAseq. Whole transcriptome analysis confirmed the division into somato- versus viscerosensory neurons, with additional evidence for subdivision of the somatic class into general and special somatosensory neurons. Cross-comparison of distinct ganglia transcriptomes identified a total of 134 markers, 113 of which are novel, which can be used to distinguish trigeminal, vestibulo-acoustic and epibranchial neuronal populations. In situ hybridisation analysis provided validation for 20/26 tested markers, and showed related expression in the target region of the hindbrain in many cases.

Conclusions: One hundred thirty-four high-confidence markers have been identified for placode-derived cranial sensory ganglia which can now be used to address the acquisition of specific cranial sensory modalities.

Keywords
Cranial sensory ganglia, Viscerosensory neuron, Somatosensory neuron, Cell type markers, Chicken
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-116738 (URN)10.1186/s13064-016-0057-y (DOI)000368768000001 ()2-s2.0-84962841554 (Scopus ID)
Available from: 2016-02-19 Created: 2016-02-11 Last updated: 2023-03-23Bibliographically approved
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