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Jess, David Unnersjö
Alternative names
Publications (8 of 8) Show all publications
Schwarz, A., Moller-Hackbarth, K., Ebarasi, L., Jess, D. U., Zambrano, S., Blom, H., . . . Patrakka, J. (2019). Coro2b, a podocyte protein downregulated in human diabetic nephropathy, is involved in the development of protamine sulphate-induced foot process effacement. Scientific Reports, 9, Article ID 8888.
Open this publication in new window or tab >>Coro2b, a podocyte protein downregulated in human diabetic nephropathy, is involved in the development of protamine sulphate-induced foot process effacement
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2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 8888Article in journal (Refereed) Published
Abstract [en]

Podocytes have an important role in the pathogenesis of diabetic nephropathy (DN). Podocyte foot process effacement, mediated largely by the actin-based cytoskeleton of foot processes, is commonly detected in DN and is believed to be a key pathogenic event in the development of proteinuria. In this study, we identified coronin 2b (Coro2b), a member of known actin-regulating proteins, the coronins, as a highly podocyte-enriched molecule located at the cytoplasmic side of the apical plasma membrane. Studies in human renal biopsies show that glomerular Coro2b expression is significantly down-regulated in patients with DN. Studies in knockout mice indicate that Coro2b is not required for the development or maintenance of the glomerular filtration barrier. Moreover, inactivation of Coro2b specifically in podocytes does not affect the outcome of nephropathy in a streptozotocin-induced diabetes model. However, Coro2b seems to modulate the reorganization of foot processes under pathological conditions as Coro2b knockout podocytes are partially protected from protamine sulfate perfusion-induced foot process effacement. Taken together, our study suggests a role for Coro2b in the pathogenesis of glomerulopathies. Further studies regarding the involvement of Coro2b in podocyte health and diseases are warranted.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2019
National Category
Biophysics
Identifiers
urn:nbn:se:kth:diva-255183 (URN)10.1038/s41598-019-45303-y (DOI)000472136900062 ()31221975 (PubMedID)2-s2.0-85067595475 (Scopus ID)
Note

QC 20190904

Available from: 2019-09-04 Created: 2019-09-04 Last updated: 2019-09-04Bibliographically approved
Jess, D. U. (2019). High-resolution Imaging of Cleared and Expanded Kidney Tissue Samples. (Doctoral dissertation). KTH Royal Institute of Technology
Open this publication in new window or tab >>High-resolution Imaging of Cleared and Expanded Kidney Tissue Samples
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The kidney is one of the most important and complex organs in the humanbody with the task of filtering hundreds of litres of blood daily. It is responsiblefor the salt and acid/base balance in the body, as well as secretinghormones important for red blood cell production and blood pressure regulation. Kidney disease is one of the fastest growing causes of death in the modern world, and this motivates extensive research for better understandingthe function of the kidney in both health and disease. Kidney failure or end stage renal disease (ESRD) is irreversible and requires treatment with dialysisor transplantation. Some of the most important cellular structures for blood filtration in the kidney are of very small dimensions (below 200 nanometers), and thus electron microscopy has previously been the only method with high enough resolution to study the morphology and topology of these minute structures. In three studies included in this thesis, we show that the finest elements of the kidney can now be resolved using different light microscopy techniques. In study 1, we show that by combining optical clearing with STED microscopy, protein localizations in the slit diaphragm of the kidney can be resolved, with widths around 75 nanometers. In study 3, a novel sample preparation method, expansion microscopy, is utilized to isotropically expand kidney tissue samples in space. Expansion improves the effective resolution by a factor of 5, making it possible to resolve podocyte foot processes and the slit diaphragmusing diffraction-limited confocal microscopy. We also show that by combining expansion microscopy and STED microscopy, the effective resolution can be improved even further (<20 nm). In our most recent work, study 5, we apply a simplified, moderate tissue swelling protocol which together with optimization of the confocal imaging provides sufficient resolution to resolve foot processes and parts of the filtration barrier. This new protocol is fast and technically simple, making it ideal for routine use, such as for future clinical pathology. In collaboration with kidney researchers, we have applied both STED microscopy and expansion microscopy to various disease models, showing that these tools can be used to both visualize and quantify pathologies occurring in different parts of the glomerular filtration barrier (GFB). In study 2, STED microscopy in combination with optical clearing is used to study the localization of Coro2b in secondary foot processes in both mouse and human tissue. In two ongoing studies with preliminary results presented in the thesis, we use STED microscopy and optical clearing to study the pathogenesis of focal segmental glomerulosclerosis (FSGS) by the use of genetic mouse models. Based on STED images, we extract different morphological parameters from foot processes and the glomerular filtration barrier (GFB) at different stages of the disease. In study 4, we apply a tissue expansion protocol to answer questions about the phenotype seen in podocytes where the mediator complex subunit 22 (Med22) is inactivated. By inactivating Med22 in a transgenic mouse line with cytosolic expression of tdTomato in podocytes, we saw strong indications that the vesicle-like structures seen in EM micrographs were indeed intracellular vesicles and not dilated sub-podocyte space. In summary, the work presented in this thesis has contributed to the development of a new toolbox for imaging renal ultra-structure using light microscopy, a field previously reserved for electron microscopy.

Place, publisher, year, edition, pages
KTH Royal Institute of Technology, 2019. p. 85
Series
TRITA-SCI-FOU ; 2019:18
Keywords
Kidney, Renal Pathology, Microscopy, Super-resolution microscopy, Tissue expansion, Foot processes, Glomerular filtration, Podocytes
National Category
Biophysics Cell Biology Cell and Molecular Biology Urology and Nephrology Medical Laboratory and Measurements Technologies
Research subject
Biological Physics
Identifiers
urn:nbn:se:kth:diva-249002 (URN)978-91-7873-163-3 (ISBN)
Public defence
2019-05-03, Air & Fire, Tomtebodavägen 23A, Solna, 09:00 (English)
Opponent
Supervisors
Note

QC 20190411

Available from: 2019-04-11 Created: 2019-04-10 Last updated: 2019-04-11Bibliographically approved
Fontana, J. M., Khodus, G. R., Unnersjö Jess, D., Blom, H., Aperia, A. & Brismar, H. (2019). Spontaneous calcium activity in metanephric mesenchymal cells regulates branching morphogenesis in the embryonic kidney. The FASEB Journal, 33(3), 4089-4096
Open this publication in new window or tab >>Spontaneous calcium activity in metanephric mesenchymal cells regulates branching morphogenesis in the embryonic kidney
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2019 (English)In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 33, no 3, p. 4089-4096Article in journal (Refereed) Published
Abstract [en]

The central role of calcium signaling during development of early vertebrates is well documented, but little is known about its role in mammalian embryogenesis. We have used immunofluorescence and time-lapse calcium imaging of cultured explanted embryonic rat kidneys to study the role of calcium signaling for branching morphogenesis. In mesenchymal cells, we recorded spontaneous calcium activity that was characterized by irregular calcium transients. The calcium signals were dependent on release of calcium from intracellular stores in the endoplasmic reticulum. Down-regulation of the calcium activity, both by blocking the sarco-endoplasmic reticulum Ca2+-ATPase and by chelating cytosolic calcium, resulted in retardation of branching morphogenesis and a reduced formation of primitive nephrons but had no effect on cell proliferation. We propose that spontaneous calcium activity contributes with a stochastic factor to the self-organizing process that controls branching morphogenesis, a major determinant of the ultimate number of nephrons in the kidney.Fontana, J. M., Khodus, G. R., Unnersjo-Jess, D., Blom, H., Aperia, A., Brismar, H. Spontaneous calcium activity in metanephric mesenchymal cells regulates branching morphogenesis in the embryonic kidney.

Place, publisher, year, edition, pages
FEDERATION AMER SOC EXP BIOL, 2019
Keywords
organogenesis, nephron, calcium imaging
National Category
Biophysics
Identifiers
urn:nbn:se:kth:diva-246250 (URN)10.1096/fj.201802054R (DOI)000459794800079 ()30496703 (PubMedID)
Note

QC 20190402

Available from: 2019-04-02 Created: 2019-04-02 Last updated: 2019-04-02Bibliographically approved
Jess, D. U., Scott, L., Sevilla, S. Z., Patrakka, J., Blom, H. & Brismar, H. (2018). Confocal super-resolution imaging of the glomerular filtration barrier enabled by tissue expansion. Kidney International, 93(4), 1008-1013
Open this publication in new window or tab >>Confocal super-resolution imaging of the glomerular filtration barrier enabled by tissue expansion
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2018 (English)In: Kidney International, ISSN 0085-2538, E-ISSN 1523-1755, Vol. 93, no 4, p. 1008-1013Article in journal (Refereed) Published
Abstract [en]

The glomerular filtration barrier, has historically only been spatially resolved using electron microscopy due to the nanometer-scale dimensions of these structures. Recently, it was shown that the nanoscale distribution of proteins in the slit diaphragm can be resolved by fluorescence based stimulated emission depletion microscopy, in combination with optical clearing. Fluorescence microscopy has advantages over electron microscopy in terms of multiplex imaging of different epitopes, and also the amount of volumetric data that can be extracted from thicker samples. However, stimulated emission depletion microscopy is still a costly technique commonly not available to most life science researchers. An imaging technique with which the glomerular filtration barrier can be visualized using more standard fluorescence imaging techniques is thus desirable. Recent studies have shown that biological tissue samples can be isotropically expanded, revealing nanoscale localizations of multiple epitopes using confocal microscopy. Here we show that kidney samples can be expanded sufficiently to study the finest elements of the filtration barrier using confocal microscopy. Thus, our result opens up the possibility to study protein distributions and foot process morphology on the effective nanometer-scale.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC, 2018
Keywords
glomerulus, imaging, podocyte, renal pathology
National Category
Atom and Molecular Physics and Optics Bioinformatics and Systems Biology
Identifiers
urn:nbn:se:kth:diva-226201 (URN)10.1016/j.kint.2017.09.019 (DOI)000428169200029 ()29241621 (PubMedID)2-s2.0-85037568536 (Scopus ID)
Note

QC 20180518

Available from: 2018-05-18 Created: 2018-05-18 Last updated: 2019-04-10Bibliographically approved
Kvedaraite, E., Lourda, M., Van Acker, A., Jess, D. U., Gavhed, D., Mjosberg, J., . . . Svensson, M. (2017). Stromal cell - innate immune cell interactions in inflammatory bowel disease patients. Paper presented at 44th Annual Meeting of the Scandinavian-Society-for-Immunology (SSI), OCT 17-20, 2017, Stockholm, SWEDEN. Scandinavian Journal of Immunology, 86(4), 253-253
Open this publication in new window or tab >>Stromal cell - innate immune cell interactions in inflammatory bowel disease patients
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2017 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 86, no 4, p. 253-253Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
WILEY, 2017
National Category
Medical Biotechnology
Identifiers
urn:nbn:se:kth:diva-215787 (URN)000411865200017 ()
Conference
44th Annual Meeting of the Scandinavian-Society-for-Immunology (SSI), OCT 17-20, 2017, Stockholm, SWEDEN
Funder
Science for Life Laboratory - a national resource center for high-throughput molecular bioscience
Note

QC 20171018

Available from: 2017-10-18 Created: 2017-10-18 Last updated: 2017-10-18Bibliographically approved
Kvedaraite, E., Jess, D. U., Gavhed, D., Idestrom, M., Svensson, M., Lourda, M. & Henter, J.-I. (2017). When Langerhans Met Crohn: A Clinical Case Report and a First Three-Dimentional Reconstruction of Human Gut. Pediatric Blood & Cancer, 64, S20-S20
Open this publication in new window or tab >>When Langerhans Met Crohn: A Clinical Case Report and a First Three-Dimentional Reconstruction of Human Gut
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2017 (English)In: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, Vol. 64, p. S20-S20Article in journal (Refereed) Published
Place, publisher, year, edition, pages
Wiley-Blackwell, 2017
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:kth:diva-214475 (URN)000408942000045 ()
Note

QC 20171011

Available from: 2017-10-11 Created: 2017-10-11 Last updated: 2017-10-11Bibliographically approved
Fontana, J. M., Jess, D. U., Blom, H., Brismar, H. & Aperia, A. (2016). Role of calcium signaling for GDNF secretion, ureter branching and early nephron formation. Paper presented at Experimental Biology Meeting, APR 02-06, 2016, San Diego, CA. The FASEB Journal, 30
Open this publication in new window or tab >>Role of calcium signaling for GDNF secretion, ureter branching and early nephron formation
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2016 (English)In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 30Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
FEDERATION AMER SOC EXP BIOL, 2016
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:kth:diva-242657 (URN)000406444705388 ()
Conference
Experimental Biology Meeting, APR 02-06, 2016, San Diego, CA
Note

QC 201902255

Available from: 2019-02-25 Created: 2019-02-25 Last updated: 2019-02-25Bibliographically approved
Rodriguez, P. Q., Chen, P., Jess, D. U., Zambrano, S. S., Guo, J., Schwarz, A., . . . Patrakka, J.Mediator complex subunit 22 is necessary for glomerular homeostasis by regulation of podocyte vesicular trafficking.
Open this publication in new window or tab >>Mediator complex subunit 22 is necessary for glomerular homeostasis by regulation of podocyte vesicular trafficking
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(English)Manuscript (preprint) (Other academic)
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:kth:diva-248127 (URN)
Note

QC 20190521

Available from: 2019-04-04 Created: 2019-04-04 Last updated: 2019-05-21Bibliographically approved
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