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Article: Notch is Not Involved in Physioxia-Mediated Stem Cell Maintenance in Midbrain Neural Stem Cells.

Herrmann, Anne / Meyer, Anne K / Braunschweig, Lena / Wagenfuehr, Lisa / Markert, Franz / Kolitsch, Deborah / Vukicevic, Vladimir / Hartmann, Christiane / Siebert, Marlen / Ehrhart-Bornstein, Monika / Hermann, Andreas / Storch, Alexander

International journal of stem cells

2023 Volume 16, Issue 3, Page(s) 293–303

Abstract: Background and objectives: The physiological oxygen tension in fetal brains (∼3%, physioxia) is beneficial for the maintenance of neural stem cells (NSCs). Sensitivity to oxygen varies between NSCs from different fetal brain regions, with midbrain NSCs ... ...

Abstract	Background and objectives: The physiological oxygen tension in fetal brains (∼3%, physioxia) is beneficial for the maintenance of neural stem cells (NSCs). Sensitivity to oxygen varies between NSCs from different fetal brain regions, with midbrain NSCs showing selective susceptibility. Data on Hif-1α/Notch regulatory interactions as well as our observations that Hif-1α and oxygen affect midbrain NSCs survival and proliferation prompted our investigations on involvement of Notch signalling in physioxia-dependent midbrain NSCs performance. Methods and results: Here we found that physioxia (3% O Conclusions: Notch signalling does not influence the fate decision of midbrain NSCs cultured
Language	English
Publishing date	2023-04-30
Publishing country	Korea (South)
Document type	Journal Article
ZDB-ID	2914134-5
ISSN	2005-5447 ; 2005-3606
ISSN (online)	2005-5447
ISSN	2005-3606
DOI	10.15283/ijsc22168
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The adrenal gland in the center.

Chavakis, T / Ehrhart-Bornstein, M

Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme

2013 Volume 45, Issue 2, Page(s) 79–80

MeSH term(s)	Adrenal Gland Diseases/congenital ; Adrenal Gland Diseases/metabolism ; Adrenal Gland Diseases/physiopathology ; Adrenal Gland Diseases/therapy ; Adrenal Glands/abnormalities ; Adrenal Glands/physiology ; Adrenal Glands/physiopathology ; Animals ; Biomedical Research/trends ; Humans ; Molecular Targeted Therapy
Language	English
Publishing date	2013-02
Publishing country	Germany
Document type	Editorial ; Introductory Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80125-2
ISSN	1439-4286 ; 0018-5043
ISSN (online)	1439-4286
ISSN	0018-5043
DOI	10.1055/s-0032-1331224
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Article: Progenitor cells in chromospheres: in response to Arthur S. Tischler.

Santana, Magda M / Ehrhart-Bornstein, Monika / Cavadas, Cláudia

Stem cells translational medicine

2013 Volume 2, Issue 12, Page(s) 1020–1021

MeSH term(s)	Adrenal Medulla/cytology ; Cell Differentiation ; Cell Proliferation ; Chromaffin Cells/metabolism ; Humans ; Stem Cells/cytology
Language	English
Publishing date	2013-11-26
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	2642270-0
ISSN	2157-6580 ; 2157-6564
ISSN (online)	2157-6580
ISSN	2157-6564
DOI	10.5966/sctm.2013-0062
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Article: The Adrenal Gland in the Center

Chavakis, T. / Ehrhart-Bornstein, M.

Hormone and Metabolic Research

2013 Volume 45, Issue 02, Page(s) 79–80

Language	English
Publishing date	2013-02-01
Publisher	© Georg Thieme Verlag KG
Publishing place	Stuttgart ; New York
Document type	Article
ZDB-ID	80125-2
ISSN	1439-4286 ; 0018-5043
ISSN (online)	1439-4286
ISSN	0018-5043
DOI	10.1055/s-0032-1331224
Database	Thieme publisher's database

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Article ; Conference proceedings: Exposure to valproic acid increases a subset of chromaffin progenitor cells within chromospheres

Vukicevic, V / Bornstein, SR / Ehrhart-Bornstein, M

Experimental and Clinical Endocrinology & Diabetes

2014

Abstract: Chromaffin cells and sympathetic neurons derive from a common sympathoadrenal progenitor cell. Recently we demonstrated the existence of chromaffin progenitor cells in the adult adrenal and their capacity to derive dopaminergic neurons in vitro. ... ...

Event/congress	57th Symposium of the German Society of Endocrinology (DGE), Dresden, 2014
Abstract	Chromaffin cells and sympathetic neurons derive from a common sympathoadrenal progenitor cell. Recently we demonstrated the existence of chromaffin progenitor cells in the adult adrenal and their capacity to derive dopaminergic neurons in vitro. Valproic acid (VA) is a histone deacetylase inhibitor that stimulates extended growth of neural stem cells. Here, we discuss the potential use of VA in improving proliferation of bovine medullary chromaffin progenitor cells. Similar to neural stem cells, chromaffin progenitors were cultured as free-floating spheroid clusters, chromospheres (CS). Treatment with VA increased proliferation of chromaffin progenitors and their enrichment within CS accompanied by an increased expression of neural progenitor markers such as nestin, Mash1, Sox1/10, Hes1. Accumulation of cells in S-phase and their increase in G 2 cell cycle phase was pronounced after treatment with VA. Our findings indicate common molecular mechanisms that control maintenance of neural and chromaffin progenitors. We observed upregulated transcription of Pitx3 and guanosine triphosphate cyclohydrolase (GTPCH), factors regulating the development of dopaminergic neurons in substantia nigra. In addition, microscopy and PCR analyses revealed increased the expression of a neural marker β III tubulin. Increased noradrenaline content indicated differentiation of postganglionic sympathetic neurons. These data indicate that VA treatment launches proliferation as well as neuronal differentiation of chromaffin progenitors in CS. The use of chromaffin progenitors as a relevant cellular source in the treatment of neurodegenerative diseases such as Parkinson's disease was discussed. The observed duality in VA action could be valuable in increasing the number of chromaffin progenitor cells and triggering their neuronal differentiation prior to grafting and contribute to the validation of chromaffin progenitor cells in treatment of neurodegenerative diseases.
Language	English
Publishing date	2014-03-05
Publishing place	Stuttgart ; New York
Document type	Article ; Conference proceedings
ZDB-ID	1225416-2
ISSN	1439-3646 ; 0947-7349
ISSN (online)	1439-3646
ISSN	0947-7349
DOI	10.1055/s-0034-1371998
Database	Thieme publisher's database

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Article: Transcription factor 7-like 2 (TCFL2) - a novel factor involved in pathogenesis of type 2 diabetes. Comment on: Grant et al., Nature Genetics 2006, Published online 15 January 2006.

Kiessling, A / Ehrhart-Bornstein, M

Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme

2006 Volume 38, Issue 2, Page(s) 137–138

MeSH term(s)	Chromosomes, Human, Pair 10/genetics ; Cohort Studies ; Diabetes Mellitus, Type 2/genetics ; Diabetes Mellitus, Type 2/metabolism ; Diabetes Mellitus, Type 2/pathology ; Genetic Markers/genetics ; Genetic Predisposition to Disease ; Humans ; Microsatellite Repeats/genetics ; Polymorphism, Genetic ; TCF Transcription Factors/genetics ; TCF Transcription Factors/metabolism ; Transcription Factor 7-Like 2 Protein
Chemical Substances	Genetic Markers ; TCF Transcription Factors ; TCF7L2 protein, human ; Transcription Factor 7-Like 2 Protein
Language	English
Publishing date	2006-02
Publishing country	Germany
Document type	Journal Article
ZDB-ID	80125-2
ISSN	1439-4286 ; 0018-5043
ISSN (online)	1439-4286
ISSN	0018-5043
DOI	10.1055/s-2006-925137
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Article ; Online: The effects of stress on brain and adrenal stem cells.

de Celis, M F R / Bornstein, S R / Androutsellis-Theotokis, A / Andoniadou, C L / Licinio, J / Wong, M-L / Ehrhart-Bornstein, M

Molecular psychiatry

2016 Volume 21, Issue 5, Page(s) 722

Language	English
Publishing date	2016-05
Publishing country	England
Document type	Published Erratum
ZDB-ID	1330655-8
ISSN	1476-5578 ; 1359-4184
ISSN (online)	1476-5578
ISSN	1359-4184
DOI	10.1038/mp.2016.26
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Zs.A 4812: Show issues

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Article ; Online: Anti-inflammatory properties of bone morphogenetic protein 4 in human adipocytes.

Baraban, E / Chavakis, T / Hamilton, B S / Sales, S / Wabitsch, M / Bornstein, S R / Ehrhart-Bornstein, M

International journal of obesity (2005)

2016 Volume 40, Issue 2, Page(s) 319–327

Abstract: Background: Obesity is characterized by increased adipocyte number and size as well as white adipose tissue (WAT) inflammation, which is fundamental for the development of insulin resistance and type-2 diabetes. These processes, regulated by various ... ...

Abstract	Background: Obesity is characterized by increased adipocyte number and size as well as white adipose tissue (WAT) inflammation, which is fundamental for the development of insulin resistance and type-2 diabetes. These processes, regulated by various endocrine, paracrine and autocrine factors, are extensively studied with the hope to interfere and to inhibit weight gain and related complications in obese patients. Recent data suggest an important role of bone morphogenic protein 4 (BMP4) in the regulation of adipogenesis and development of obesity. BMP4 is a growth factor of the transforming growth factor-β superfamily. Initially, BMPs were identified as inducers of ectopic bone formation. It is now apparent, however, that these proteins have different pleiotropic developmental actions and including playing a role in white adipogenesis. Methods and results: Here, we demonstrate that the expression of BMP4 in human WAT is negatively correlated to body mass index and to the expression of pro-inflammatory cytokines. In vitro, BMP4 expression in cultured human adipocytes is upregulated after induction of differentiation. Cells treated with exogenous BMP4 increased peroxisome proliferator-activated receptor γ (PPARγ) expression and significantly reduced the expression of pro-inflammatory cytokines including tumor necrosis factor α (TNF-α) and monocyte chemoattractant protein 1. TNF-α treatment of fully differentiated adipocytes resulted in downregulation of the expression of adipogenic genes and elevated expression of pro-inflammatory cytokines. Exogenous BMP4 addition significantly reduced the negative effect of TNF-α on the expression profile of adipocytes. Finally, treatment of human adipocytes with exogenous BMP4 reduced the adipocytes' chemoattractant potential and the migration of monocytes toward adipocyte-conditioned medium. Conclusions: These results indicate that BMP4 is an important anti-inflammatory molecule, which may act through PPARγ and reduces TNF-α-mediated pro-inflammatory cytokine production in human adipocytes. Through its anti-inflammatory potential, BMP4 may serve as a protective factor for inflammation-related diseases such as insulin-tolerance or type-2 diabetes.
MeSH term(s)	Adipocytes/metabolism ; Adipogenesis ; Adipose Tissue, White/metabolism ; Anti-Inflammatory Agents/pharmacology ; Bone Morphogenetic Protein 4/metabolism ; Bone Morphogenetic Protein 4/pharmacology ; Cell Differentiation/physiology ; Cell Movement/physiology ; Diabetes Mellitus, Type 2/metabolism ; Diabetes Mellitus, Type 2/physiopathology ; Humans ; Inflammation/metabolism ; Inflammation/physiopathology ; Insulin Resistance ; Obesity/metabolism ; Obesity/physiopathology ; Signal Transduction/physiology ; Tumor Necrosis Factor-alpha/metabolism
Chemical Substances	Anti-Inflammatory Agents ; BMP4 protein, human ; Bone Morphogenetic Protein 4 ; Tumor Necrosis Factor-alpha
Language	English
Publishing date	2016-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	752409-2
ISSN	1476-5497 ; 0307-0565
ISSN (online)	1476-5497
ISSN	0307-0565
DOI	10.1038/ijo.2015.141
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Article ; Online: Calcium-dependent release of adipocyte fatty acid binding protein from human adipocytes.

Schlottmann, I / Ehrhart-Bornstein, M / Wabitsch, M / Bornstein, S R / Lamounier-Zepter, V

International journal of obesity (2005)

2013 Volume 38, Issue 9, Page(s) 1221–1227

Abstract: Background: Fatty acid binding protein 4 (FABP4) is a predominantly cytosolic protein of the adipocytes, but also abundantly present in human plasma; its plasma concentrations were linked to obesity and metabolic syndrome. Recent studies have suggested ... ...

Abstract	Background: Fatty acid binding protein 4 (FABP4) is a predominantly cytosolic protein of the adipocytes, but also abundantly present in human plasma; its plasma concentrations were linked to obesity and metabolic syndrome. Recent studies have suggested a direct extracellular effect of FABP4 in the regulation of glucose metabolism and heart function independently of its effect as a carrier protein. Interestingly, FABP4 has no secretory signal sequence; hence, the mechanisms how FABP4 is released from adipocytes are unclear. Methods and results: In this study we investigated the mechanisms for FABP4 secretion from human adipocytes by using isolated primary pre-adipocytes (PAs) and the human adipocyte cell strain Simpson-Golabi-Behmel syndrome. In undifferentiated PAs, FABP4 expression was barely detectable and increased continuously during differentiation. The increase in FABP4 mRNA expression was accompanied by high levels of FABP4 secretion. In differentiated human adipocytes, FABP4 secretion was not abolished by blocking the Golgi-dependent secretory pathway in vitro, supporting a non-classical secretion mechanism for FABP4. However, raising intracellular Ca(2+) levels enhanced FABP4 secretion in a concentration-dependent manner. Conclusion: This study shows that FABP4 is actively released from human adipocytes in vitro via a non-classical, calcium-dependent mechanism.
MeSH term(s)	Adipocytes/metabolism ; Arrhythmias, Cardiac/metabolism ; Arrhythmias, Cardiac/physiopathology ; Calcium/metabolism ; Calcium Signaling ; Cell Differentiation ; Cells, Cultured ; Fatty Acid-Binding Proteins/metabolism ; Genetic Diseases, X-Linked/metabolism ; Genetic Diseases, X-Linked/physiopathology ; Gigantism/metabolism ; Gigantism/physiopathology ; Heart Defects, Congenital/metabolism ; Heart Defects, Congenital/physiopathology ; Humans ; Intellectual Disability/metabolism ; Intellectual Disability/physiopathology ; Metabolic Syndrome/metabolism ; Metabolic Syndrome/physiopathology ; Obesity/metabolism ; Obesity/physiopathology ; RNA, Messenger ; Reverse Transcriptase Polymerase Chain Reaction
Chemical Substances	FABP4 protein, human ; Fatty Acid-Binding Proteins ; RNA, Messenger ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2013-12-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	752409-2
ISSN	1476-5497 ; 0307-0565
ISSN (online)	1476-5497
ISSN	0307-0565
DOI	10.1038/ijo.2013.241
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Article ; Online: Secretion and signaling activities of lipoprotein-associated hedgehog and non-sterol-modified hedgehog in flies and mammals.

Palm, Wilhelm / Swierczynska, Marta M / Kumari, Veena / Ehrhart-Bornstein, Monika / Bornstein, Stefan R / Eaton, Suzanne

PLoS biology

2013 Volume 11, Issue 3, Page(s) e1001505

Abstract: Hedgehog (Hh) proteins control animal development and tissue homeostasis. They activate gene expression by regulating processing, stability, and activation of Gli/Cubitus interruptus (Ci) transcription factors. Hh proteins are secreted and spread through ...

Abstract	Hedgehog (Hh) proteins control animal development and tissue homeostasis. They activate gene expression by regulating processing, stability, and activation of Gli/Cubitus interruptus (Ci) transcription factors. Hh proteins are secreted and spread through tissue, despite becoming covalently linked to sterol during processing. Multiple mechanisms have been proposed to release Hh proteins in distinct forms; in Drosophila, lipoproteins facilitate long-range Hh mobilization but also contain lipids that repress the pathway. Here, we show that mammalian lipoproteins have conserved roles in Sonic Hedgehog (Shh) release and pathway repression. We demonstrate that lipoprotein-associated forms of Hh and Shh specifically block lipoprotein-mediated pathway inhibition. We also identify a second conserved release form that is not sterol-modified and can be released independently of lipoproteins (Hh-N/Shh-N). Lipoprotein-associated Hh/Shh and Hh-N/Shh-N have complementary and synergistic functions. In Drosophila wing imaginal discs, lipoprotein-associated Hh increases the amount of full-length Ci, but is insufficient for target gene activation. However, small amounts of non-sterol-modified Hh synergize with lipoprotein-associated Hh to fully activate the pathway and allow target gene expression. The existence of Hh secretion forms with distinct signaling activities suggests a novel mechanism for generating a diversity of Hh responses.
MeSH term(s)	Animals ; Drosophila ; Drosophila Proteins/metabolism ; HeLa Cells ; Hedgehog Proteins/metabolism ; Humans ; Immunoprecipitation ; Lipoproteins/metabolism ; Mammals ; Signal Transduction/genetics ; Signal Transduction/physiology ; Transcription Factors/metabolism ; Zinc Finger Protein GLI1
Chemical Substances	Drosophila Proteins ; GLI1 protein, human ; Hedgehog Proteins ; Lipoproteins ; Transcription Factors ; Zinc Finger Protein GLI1
Language	English
Publishing date	2013-03-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2126776-5
ISSN	1545-7885 ; 1544-9173
ISSN (online)	1545-7885
ISSN	1544-9173
DOI	10.1371/journal.pbio.1001505
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