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Article ; Online: Exploiting meta-analysis of genome-wide interaction with serum 25-hydroxyvitamin D to identify novel genetic loci associated with pulmonary function.

Seo, Jungkyun / Gaddis, Nathan C / Patchen, Bonnie K / Xu, Jiayi / Barr, R Graham / O'Connor, George / Manichaikul, Ani W / Gharib, Sina A / Dupuis, Josée / North, Kari E / Cassano, Patricia A / Hancock, Dana B

The American journal of clinical nutrition

2024

Abstract: Background: Higher 25-hydroxyvitamin D (25(OH)D) concentrations in serum has a positive ... association with pulmonary function. Investigating genome-wide interactions with 25(OH)D may reveal new ... associated with pulmonary function by accounting for 25(OH)D interactions.: Methods: We included 211,264 ...

Abstract	Background: Higher 25-hydroxyvitamin D (25(OH)D) concentrations in serum has a positive association with pulmonary function. Investigating genome-wide interactions with 25(OH)D may reveal new biological insights into pulmonary function. Objectives: We aimed to identify novel genetic variants associated with pulmonary function by accounting for 25(OH)D interactions. Methods: We included 211,264 participants from the observational United Kingdom Biobank study with pulmonary function tests (PFTs), genome-wide genotypes, and 25(OH)D concentrations from 4 ancestral backgrounds-European, African, East Asian, and South Asian. Among PFTs, we focused on forced expiratory volume in the first second (FEV Results: Our GWAS meta-analyses, accounting for interaction with 25(OH)D, revealed 30 genetic variants significantly associated with FEV Conclusion: Genetic variant associations with lung function can be modified by 25(OH)D, and smoking history can further modify variant×25(OH)D interactions. These results expand the known genetic architecture of pulmonary function and add evidence that gene-environment interactions, including with 25(OH)D and smoking, influence lung function.
Language	English
Publishing date	2024-03-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	280048-2
ISSN	1938-3207 ; 0002-9165
ISSN (online)	1938-3207
ISSN	0002-9165
DOI	10.1016/j.ajcnut.2024.03.007
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Article ; Online: No association between ACTN3 R577X and ACE I/D polymorphisms and endurance running times in 698 Caucasian athletes.

Papadimitriou, Ioannis D / Lockey, Sarah J / Voisin, Sarah / Herbert, Adam J / Garton, Fleur / Houweling, Peter J / Cieszczyk, Pawel / Maciejewska-Skrendo, Agnieszka / Sawczuk, Marek / Massidda, Myosotis / Calò, Carla Maria / Astratenkova, Irina V / Kouvatsi, Anastasia / Druzhevskaya, Anastasiya M / Jacques, Macsue / Ahmetov, Ildus I / Stebbings, Georgina K / Heffernan, Shane / Day, Stephen H /

Erskine, Robert / Pedlar, Charles / Kipps, Courtney / North, Kathryn N / Williams, Alun G / Eynon, Nir

BMC genomics

2018 Volume 19, Issue 1, Page(s) 13

Abstract: Background: Studies investigating associations between ACTN3 R577X and ACE I/D genotypes and ... quantitative measures of performance.: Aim: To examine the association between ACTN3 R577X and ACE I/D ... R577X or ACE I/D genotype and running performance at any distance in men or women. Mean (SD) marathon ...

Abstract	Background: Studies investigating associations between ACTN3 R577X and ACE I/D genotypes and endurance athletic status have been limited by small sample sizes from mixed sport disciplines and lack quantitative measures of performance. Aim: To examine the association between ACTN3 R577X and ACE I/D genotypes and best personal running times in a large homogeneous cohort of endurance runners. Methods: We collected a total of 1064 personal best 1500, 3000, 5000 m and marathon running times of 698 male and female Caucasian endurance athletes from six countries (Australia, Greece, Italy, Poland, Russia and UK). Athletes were genotyped for ACTN3 R577X and ACE ID variants. Results: There was no association between ACTN3 R577X or ACE I/D genotype and running performance at any distance in men or women. Mean (SD) marathon times (in s) were for men: ACTN3 RR 9149 (593), RX 9221 (582), XX 9129 (582) p = 0.94; ACE DD 9182 (665), ID 9214 (549), II 9155 (492) p = 0.85; for women: ACTN3 RR 10796 (818), RX 10667 (695), XX 10675 (553) p = 0.36; ACE DD 10604 (561), ID 10766 (740), II 10771 (708) p = 0.21. Furthermore, there were no associations between these variants and running time for any distance in a sub-analysis of athletes with personal records within 20% of world records. Conclusions: Thus, consistent with most case-control studies, this multi-cohort quantitative analysis demonstrates it is unlikely that ACTN3 XX genotype provides an advantage in competitive endurance running performance. For ACE II genotype, some prior studies show an association but others do not. Our data indicate it is also unlikely that ACE II genotype provides an advantage in endurance running.
MeSH term(s)	Actinin/genetics ; Athletes ; European Continental Ancestry Group/genetics ; Female ; Genotype ; Humans ; Male ; Peptidyl-Dipeptidase A/genetics ; Physical Endurance/genetics ; Polymorphism, Genetic ; Running/physiology
Chemical Substances	ACTN3 protein, human ; Actinin (11003-00-2) ; Peptidyl-Dipeptidase A (EC 3.4.15.1)
Language	English
Publishing date	2018--03
Publishing country	England
Document type	Journal Article
ISSN	1471-2164
ISSN (online)	1471-2164
DOI	10.1186/s12864-017-4412-0
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Article: Assessing the contribution of understory sun-induced chlorophyll fluorescence through 3-D radiative transfer modelling and field data

Hornero, A / North, P.R.J / Zarco-Tejada, P.J / Rascher, U / Martín, M.P / Migliavacca, M / Hernandez-Clemente, R

Remote sensing of environment. 2021 Feb., v. 253

2021

Abstract: A major international effort has been made to monitor sun-induced chlorophyll fluorescence (SIF) from space as a proxy for the photosynthetic activity of terrestrial vegetation. However, the effect of spatial heterogeneity on the SIF retrievals from ... ...

Abstract	A major international effort has been made to monitor sun-induced chlorophyll fluorescence (SIF) from space as a proxy for the photosynthetic activity of terrestrial vegetation. However, the effect of spatial heterogeneity on the SIF retrievals from canopy radiance derived from images with medium and low spatial resolution remains uncharacterised. In images from forest and agricultural landscapes, the background comprises a mixture of soil and understory and can generate confounding effects that limit the interpretation of the SIF at the canopy level. This paper aims to improve the understanding of SIF from coarse spatial resolutions in heterogeneous canopies by considering the separated contribution of tree crowns, understory and background components, using a modified version of the FluorFLIGHT radiative transfer model (RTM). The new model is compared with others through the RAMI model intercomparison framework and is validated with airborne data. The airborne campaign includes high-resolution data collected over a tree-grass ecosystem with the HyPlant imaging spectrometer within the FLuorescence EXplorer (FLEX) preparatory missions. Field data measurements were collected from plots with a varying fraction of tree and understory vegetation cover. The relationship between airborne SIF calculated from pure tree crowns and aggregated pixels shows the effect of the understory at different resolutions. For a pixel size smaller than the mean crown size, the impact of the background was low (R² > 0.99; NRMSE < 0.01). By contrast, for a pixel size larger than the crown size, the goodness of fit decreased (R² < 0.6; NRMSE > 0.2). This study demonstrates that using a 3D RTM model improves the calculation of SIF significantly (R² = 0.83, RMSE = 0.03 mW m⁻² sr⁻¹ nm⁻¹) when the specific contribution of the soil and understory layers are accounted for, in comparison with the SIF calculated from mixed pixels that considers only one layer as background (R² = 0.4, RMSE = 0.28 mW m⁻² sr⁻¹ nm⁻¹). These results demonstrate the need to account for the contribution of SIF emitted by the understory in the quantification of SIF within tree crowns and within the canopy from aggregated pixels in heterogeneous forest canopies.
Keywords	chlorophyll ; ecosystems ; environment ; fluorescence ; forests ; models ; photosynthesis ; radiative transfer ; soil ; spatial variation ; spectrometers ; trees ; understory ; vegetation cover
Language	English
Dates of publication	2021-02
Publishing place	Elsevier Inc.
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	431483-9
ISSN	0034-4257
ISSN	0034-4257
DOI	10.1016/j.rse.2020.112195
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: ACTN3 R577X and ACE I/D gene variants influence performance in elite sprinters: a multi-cohort study.

Papadimitriou, Ioannis D / Lucia, Alejandro / Pitsiladis, Yannis P / Pushkarev, Vladimir P / Dyatlov, Dmitry A / Orekhov, Evgeniy F / Artioli, Guilherme G / Guilherme, João Paulo L F / Lancha, Antonio H / Ginevičienė, Valentina / Cieszczyk, Pawel / Maciejewska-Karlowska, Agnieszka / Sawczuk, Marek / Muniesa, Carlos A / Kouvatsi, Anastasia / Massidda, Myosotis / Calò, Carla Maria / Garton, Fleur / Houweling, Peter J /

Wang, Guan / Austin, Krista / Druzhevskaya, Anastasiya M / Astratenkova, Irina V / Ahmetov, Ildus I / Bishop, David J / North, Kathryn N / Eynon, Nir

BMC genomics

2016 Volume 17, Page(s) 285

Abstract: Background: To date, studies investigating the association between ACTN3 R577X and ACE I/D gene ... allele and ACE D allele dominant model account for 0.92 % and 1.48 % of sprint time variance ...

Abstract	Background: To date, studies investigating the association between ACTN3 R577X and ACE I/D gene variants and elite sprint/power performance have been limited by small cohorts from mixed sport disciplines, without quantitative measures of performance. Aim: To examine the association between these variants and sprint time in elite athletes. Methods: We collected a total of 555 best personal 100-, 200-, and 400-m times of 346 elite sprinters in a large cohort of elite Caucasian or African origin sprinters from 10 different countries. Sprinters were genotyped for ACTN3 R577X and ACE ID variants. Results: On average, male Caucasian sprinters with the ACTN3 577RR or the ACE DD genotype had faster best 200-m sprint time than their 577XX (21.19 ± 0.53 s vs. 21.86 ± 0.54 s, p = 0.016) and ACE II (21.33 ± 0.56 vs. 21.93 ± 0.67 sec, p = 0.004) counterparts and only one case of ACE II, and no cases of ACTN3 577XX, had a faster 200-m time than the 2012 London Olympics qualifying (vs. 12 qualified sprinters with 577RR or 577RX genotype). Caucasian sprinters with the ACE DD genotype had faster best 400-m sprint time than their ACE II counterparts (46.94 ± 1.19 s vs. 48.50 ± 1.07 s, p = 0.003). Using genetic models we found that the ACTN3 577R allele and ACE D allele dominant model account for 0.92 % and 1.48 % of sprint time variance, respectively. Conclusions: Despite sprint performance relying on many gene variants and environment, the % sprint time variance explained by ACE and ACTN3 is substantial at the elite level and might be the difference between a world record and only making the final.
MeSH term(s)	Actinin/genetics ; African Continental Ancestry Group ; Alleles ; Athletes ; Athletic Performance ; Cohort Studies ; European Continental Ancestry Group ; Female ; Genotype ; Humans ; Male ; Peptidyl-Dipeptidase A/genetics ; Polymorphism, Genetic ; Running
Chemical Substances	ACTN3 protein, human ; Actinin (11003-00-2) ; ACE protein, human (EC 3.4.15.1) ; Peptidyl-Dipeptidase A (EC 3.4.15.1)
Language	English
Publishing date	2016-04-13
Publishing country	England
Document type	Journal Article
ISSN	1471-2164
ISSN (online)	1471-2164
DOI	10.1186/s12864-016-2462-3
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Validating a 1-D SVAT model in a range of USA and Australian ecosystems

G. P. Petropoulos / M. R. North / G. Ireland / P. K. Srivastava / D. V. Rendall

Geoscientific Model Development Discussions, Vol 8, Iss 3, Pp 2437-

evidence towards its use as a tool to study Earth's system interactions

2015 Volume 2495

Abstract: This paper describes the validation of the SimSphere SVAT model conducted at different ecosystem types in the USA and Australia. Specific focus was given to examining the models' ability in predicting Shortwave Incoming Solar Radiation ( R g ), Net ... ...

Abstract	This paper describes the validation of the SimSphere SVAT model conducted at different ecosystem types in the USA and Australia. Specific focus was given to examining the models' ability in predicting Shortwave Incoming Solar Radiation ( R g ), Net Radiation ( R net ), Latent Heat (LE), Sensible Heat ( H ), Air Temperature at 1.3 m ( T air 1.3 m ) and Air Temperature at 50 m ( T air 50 m ). Model predictions were compared against corresponding in situ measurements acquired for a total of 72 selected days of the year 2011 obtained from 8 sites belonging to the AmeriFlux (USA) and OzFlux (Australia) monitoring networks. Selected sites were representative of a variety of environmental, biome and climatic conditions, to allow for the inclusion of contrasting conditions in the model evaluation. The application of the model confirmed its high capability in representing the multifarious and complex interactions of the Earth system. Comparisons showed a good agreement between modelled and measured fluxes, especially for the days with smoothed daily flux trends. A good to excellent agreement between the model predictions and the in situ measurements was reported, particularly so for the LE, H , T 1.3 m and T 50 m parameters (RMSD = 39.47, 55.06 W m −2 , 3.23, 3.77 °C respectively). A systematic underestimation of R g and R net (RMSD = 67.83, 58.69 W m −2 , MBE = 67.83, 58.69 W m −2 respectively) was also found. Highest simulation accuracies were obtained for the open woodland savannah and mulga woodland sites for most of the compared parameters. Very high values of the Nash–Sutcliffe efficiency index were also reported for all parameters ranging from 0.720 to 0.998, suggesting a very good model representation of the observations. To our knowledge, this study presents the first comprehensive validation of SimSphere, particularly so in USA and Australian ecosystem types. Findings are important and timely, given the rapidly expanding use of this model worldwide both as an educational and research tool. This includes ongoing research by different Space Agencies examining its synergistic use with Earth Observation data towards the development of global operational products.
Keywords	Geology ; QE1-996.5 ; Science ; Q ; Geography (General) ; G1-922
Subject code	333
Language	English
Publishing date	2015-03-01T00:00:00Z
Publisher	Copernicus Publications
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Developmental Vitamin D Availability Impacts Hematopoietic Stem Cell Production.

Cortes, Mauricio / Chen, Michael J / Stachura, David L / Liu, Sarah Y / Kwan, Wanda / Wright, Francis / Vo, Linda T / Theodore, Lindsay N / Esain, Virginie / Frost, Isaura M / Schlaeger, Thorsten M / Goessling, Wolfram / Daley, George Q / North, Trista E

Cell reports

2016 Volume 17, Issue 2, Page(s) 458–468

Abstract: Vitamin D insufficiency is a worldwide epidemic affecting billions of individuals, including ... mediated biosynthesis or vitamin D receptor (VDR) function by gene knockdown resulted in significantly ...

Abstract	Vitamin D insufficiency is a worldwide epidemic affecting billions of individuals, including pregnant women and children. Despite its high incidence, the impact of active vitamin D3 (1,25(OH)D3) on embryonic development beyond osteo-regulation remains largely undefined. Here, we demonstrate that 1,25(OH)D3 availability modulates zebrafish hematopoietic stem and progenitor cell (HSPC) production. Loss of Cyp27b1-mediated biosynthesis or vitamin D receptor (VDR) function by gene knockdown resulted in significantly reduced runx1 expression and Flk1
MeSH term(s)	Animals ; Biological Availability ; Calcium Signaling/genetics ; Core Binding Factor Alpha 2 Subunit/genetics ; Cytochrome P-450 Enzyme System/genetics ; Embryonic Development/genetics ; Female ; Gene Expression Regulation, Developmental ; Hematopoiesis/genetics ; Hematopoietic Stem Cells/metabolism ; Humans ; Interleukin-8/genetics ; Interleukin-8/metabolism ; Pregnancy ; Receptors, Calcitriol/genetics ; Vascular Endothelial Growth Factor Receptor-2/genetics ; Vitamin D/genetics ; Vitamin D/metabolism ; Vitamin D Deficiency/genetics ; Vitamin D Deficiency/metabolism ; Zebrafish/genetics ; Zebrafish/growth & development ; Zebrafish Proteins/genetics
Chemical Substances	Core Binding Factor Alpha 2 Subunit ; Interleukin-8 ; Receptors, Calcitriol ; Zebrafish Proteins ; runx1 protein, zebrafish ; Vitamin D (1406-16-2) ; Cytochrome P-450 Enzyme System (9035-51-2) ; Cyp27c1 protein, zebrafish (EC 1.-) ; Vascular Endothelial Growth Factor Receptor-2 (EC 2.7.10.1)
Language	English
Publishing date	2016-10-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2016.09.012
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Article: Monitoring the incidence of Xylella fastidiosa infection in olive orchards using ground-based evaluations, airborne imaging spectroscopy and Sentinel-2 time series through 3-D radiative transfer modelling

Hornero, A / Hernández-Clemente, R / North, P.R.J / Beck, P.S.A / Boscia, D / Navas-Cortes, J.A / Zarco-Tejada, P.J

Remote sensing of environment. 2020 Jan., v. 236

2020

Abstract: ... we combined 3-D radiative transfer modelling (3D-RTM), which accounts for the seasonal background variations ...

Abstract	Outbreaks of Xylella fastidiosa (Xf) in Europe generate considerable economic and environmental damage, and this plant pest continues to spread. Detecting and monitoring the spatio-temporal dynamics of the disease symptoms caused by Xf at a large scale is key to curtailing its expansion and mitigating its impacts. Here, we combined 3-D radiative transfer modelling (3D-RTM), which accounts for the seasonal background variations, with passive optical satellite data to assess the spatio-temporal dynamics of Xf infections in olive orchards. We developed a 3D-RTM approach to predict Xf infection incidence in olive orchards, integrating airborne hyperspectral imagery and freely available Sentinel-2 satellite data with radiative transfer modelling and field observations. Sentinel-2A time series data collected over a two-year period were used to assess the temporal trends in Xf-infected olive orchards in the Apulia region of southern Italy. Hyperspectral images spanning the same two-year period were used for validation, along with field surveys; their high resolution also enabled the extraction of soil spectrum variations required by the 3D-RTM to account for canopy background effect. Temporal changes were validated with more than 3000 trees from 16 orchards covering a range of disease severity (DS) and disease incidence (DI) levels. Among the wide range of structural and physiological vegetation indices evaluated from Sentinel-2 imagery, the temporal variation of the Atmospherically Resistant Vegetation Index (ARVI) and Optimized Soil-Adjusted Vegetation Index (OSAVI) showed superior performance for DS and DI estimation (r²VALUES>0.7, p < 0.001). When seasonal understory changes were accounted for using modelling methods, the error of DI prediction was reduced 3-fold. Thus, we conclude that the retrieval of DI through model inversion and Sentinel-2 imagery can form the basis for operational vegetation damage monitoring worldwide. Our study highlight the value of interpreting temporal variations in model retrievals to detect anomalies in vegetation health.
Keywords	Olea europaea ; Xylella fastidiosa ; bacterial diseases of plants ; canopy ; disease incidence ; disease severity ; hyperspectral imagery ; image analysis ; models ; monitoring ; olives ; orchards ; pests ; plant pathogenic bacteria ; prediction ; radiative transfer ; remote sensing ; soil ; spectroscopy ; surveys ; temporal variation ; time series analysis ; trees ; understory ; vegetation ; vegetation index ; Italy
Language	English
Dates of publication	2020-01
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	431483-9
ISSN	0034-4257
ISSN	0034-4257
DOI	10.1016/j.rse.2019.111480
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Meta-analysis across Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium provides evidence for an association of serum vitamin D with pulmonary function.

Xu, Jiayi / Bartz, Traci M / Chittoor, Geetha / Eiriksdottir, Gudny / Manichaikul, Ani W / Sun, Fangui / Terzikhan, Natalie / Zhou, Xia / Booth, Sarah L / Brusselle, Guy G / de Boer, Ian H / Fornage, Myriam / Frazier-Wood, Alexis C / Graff, Mariaelisa / Gudnason, Vilmundur / Harris, Tamara B / Hofman, Albert / Hou, Ruixue / Houston, Denise K /

Jacobs, David R / Kritchevsky, Stephen B / Latourelle, Jeanne / Lemaitre, Rozenn N / Lutsey, Pamela L / O'Connor, George / Oelsner, Elizabeth C / Pankow, James S / Psaty, Bruce M / Rohde, Rebecca R / Rich, Stephen S / Rotter, Jerome I / Smith, Lewis J / Stricker, Bruno H / Voruganti, V Saroja / Wang, Thomas J / Zillikens, M Carola / Barr, R Graham / Dupuis, Josée / Gharib, Sina A / Lahousse, Lies / London, Stephanie J / North, Kari E / Smith, Albert V / Steffen, Lyn M / Hancock, Dana B / Cassano, Patricia A

The British journal of nutrition

2018 Volume 120, Issue 10, Page(s) 1159–1170

Abstract: The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies ... reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)-pulmonary function association ... We conducted the largest cross-sectional meta-analysis of the 25(OH)D-pulmonary function association to date ...

Abstract	The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)-pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D-pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (P race difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (P race difference=0·56). Among EA, the 25(OH)D-FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
MeSH term(s)	Adult ; Aged ; Aging ; Black People ; Cross-Sectional Studies ; Female ; Forced Expiratory Volume ; Genome, Human ; Heart/physiology ; Heart Diseases/genetics ; Heart Diseases/prevention & control ; Humans ; Lung/physiology ; Lung Diseases/genetics ; Lung Diseases/prevention & control ; Male ; Middle Aged ; Molecular Epidemiology ; Prospective Studies ; Regression Analysis ; Respiratory Function Tests ; Smoking ; Vital Capacity ; Vitamin D/analogs & derivatives ; Vitamin D/blood ; White People
Chemical Substances	Vitamin D (1406-16-2) ; 25-hydroxyvitamin D (A288AR3C9H)
Language	English
Publishing date	2018-09-12
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	280396-3
ISSN	1475-2662 ; 0007-1145
ISSN (online)	1475-2662
ISSN	0007-1145
DOI	10.1017/S0007114518002180
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Article ; Online: Accumulation of the Vitamin D Precursor Cholecalciferol Antagonizes Hedgehog Signaling to Impair Hemogenic Endothelium Formation.

Cortes, Mauricio / Liu, Sarah Y / Kwan, Wanda / Alexa, Kristen / Goessling, Wolfram / North, Trista E

Stem cell reports

2015 Volume 5, Issue 4, Page(s) 471–479

Abstract: ... we demonstrate that the vitamin D precursor cholecalciferol (D3) modulates HSPC production by impairing hemogenic ... binding domain of Smoothened. These findings highlight a direct impact of inefficient vitamin D synthesis ...

Abstract	Hematopoietic stem and progenitor cells (HSPCs) are born from hemogenic endothelium in the dorsal aorta. Specification of this hematopoietic niche is regulated by a signaling axis using Hedgehog (Hh) and Notch, which culminates in expression of Runx1 in the ventral wall of the artery. Here, we demonstrate that the vitamin D precursor cholecalciferol (D3) modulates HSPC production by impairing hemogenic vascular niche formation. Accumulation of D3 through exogenous treatment or inhibition of Cyp2r1, the enzyme required for D3 25-hydroxylation, results in Hh pathway antagonism marked by loss of Gli-reporter activation, defects in vascular niche identity, and reduced HSPCs. Mechanistic studies indicated the effect was specific to D3, and not active 1,25-dihydroxy vitamin D3, acting on the extracellular sterol-binding domain of Smoothened. These findings highlight a direct impact of inefficient vitamin D synthesis on cell fate commitment and maturation in Hh-regulated tissues, which may have implications beyond hemogenic endothelium specification.
MeSH term(s)	Animals ; Cholecalciferol/metabolism ; Cholecalciferol/pharmacology ; Cholestanetriol 26-Monooxygenase/genetics ; Cholestanetriol 26-Monooxygenase/metabolism ; Gene Deletion ; Hedgehog Proteins/metabolism ; Hematopoiesis/drug effects ; Hematopoietic Stem Cells/cytology ; Hematopoietic Stem Cells/drug effects ; Receptors, G-Protein-Coupled/metabolism ; Signal Transduction/drug effects ; Smoothened Receptor ; Vitamins/metabolism ; Vitamins/pharmacology ; Zebrafish/embryology ; Zebrafish/genetics ; Zebrafish/metabolism ; Zebrafish Proteins/genetics ; Zebrafish Proteins/metabolism
Chemical Substances	Hedgehog Proteins ; Receptors, G-Protein-Coupled ; Smoothened Receptor ; Vitamins ; Zebrafish Proteins ; smo protein, zebrafish ; Cholecalciferol (1C6V77QF41) ; Cholestanetriol 26-Monooxygenase (EC 1.14.15.15)
Language	English
Publishing date	2015-09-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2720528-9
ISSN	2213-6711 ; 2213-6711
ISSN (online)	2213-6711
ISSN	2213-6711
DOI	10.1016/j.stemcr.2015.08.010
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Article ; Online: Developmental Vitamin D Availability Impacts Hematopoietic Stem Cell Production

Mauricio Cortes / Michael J. Chen / David L. Stachura / Sarah Y. Liu / Wanda Kwan / Francis Wright / Linda T. Vo / Lindsay N. Theodore / Virginie Esain / Isaura M. Frost / Thorsten M. Schlaeger / Wolfram Goessling / George Q. Daley / Trista E. North

Cell Reports, Vol 17, Iss 2, Pp 458-

2016 Volume 468

Abstract	Vitamin D insufficiency is a worldwide epidemic affecting billions of individuals, including pregnant women and children. Despite its high incidence, the impact of active vitamin D3 (1,25(OH)D3) on embryonic development beyond osteo-regulation remains largely undefined. Here, we demonstrate that 1,25(OH)D3 availability modulates zebrafish hematopoietic stem and progenitor cell (HSPC) production. Loss of Cyp27b1-mediated biosynthesis or vitamin D receptor (VDR) function by gene knockdown resulted in significantly reduced runx1 expression and Flk1+cMyb+ HSPC numbers. Selective modulation in vivo and in vitro in zebrafish indicated that vitamin D3 acts directly on HSPCs, independent of calcium regulation, to increase proliferation. Notably, ex vivo treatment of human HSPCs with 1,25(OH)D3 also enhanced hematopoietic colony numbers, illustrating conservation across species. Finally, gene expression and epistasis analysis indicated that CXCL8 (IL-8) was a functional target of vitamin D3-mediated HSPC regulation. Together, these findings highlight the relevance of developmental 1,25(OH)D3 availability for definitive hematopoiesis and suggest potential therapeutic utility in HSPC expansion.
Keywords	vitamin D ; 1,25(OH)D3 ; hematopoietic stem cell (HSC) ; cxcl8 ; zebrafish ; hUCB ; CFU-C ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2016-10-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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