Publications by authors named "J C M Dekkers"

359 Publications

Revealing the spatio-phenotypic patterning of cells in healthy and tumor tissues with mLSR-3D and STAPL-3D.

Nat Biotechnol 2021 Jun 3. Epub 2021 Jun 3.

Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.

Despite advances in three-dimensional (3D) imaging, it remains challenging to profile all the cells within a large 3D tissue, including the morphology and organization of the many cell types present. Here, we introduce eight-color, multispectral, large-scale single-cell resolution 3D (mLSR-3D) imaging and image analysis software for the parallelized, deep learning-based segmentation of large numbers of single cells in tissues, called segmentation analysis by parallelization of 3D datasets (STAPL-3D). Applying the method to pediatric Wilms tumor, we extract molecular, spatial and morphological features of millions of cells and reconstruct the tumor's spatio-phenotypic patterning. In situ population profiling and pseudotime ordering reveals a highly disorganized spatial pattern in Wilms tumor compared to healthy fetal kidney, yet cellular profiles closely resembling human fetal kidney cells could be observed. In addition, we identify previously unreported tumor-specific populations, uniquely characterized by their spatial embedding or morphological attributes. Our results demonstrate the use of combining mLSR-3D and STAPL-3D to generate a comprehensive cellular map of human tumors.
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http://dx.doi.org/10.1038/s41587-021-00926-3DOI Listing
June 2021

Proliferation of Peripheral Blood Mononuclear Cells From Healthy Piglets After Mitogen Stimulation As Indicators of Disease Resilience.

J Anim Sci 2021 May 4. Epub 2021 May 4.

Department of Large Animal Clinical Sciences, University of Saskatchewan, Saskatoon, SK, Canada.

Disease resilience refers to productivity of an animal under disease. Given the high biosecurity of pig nucleus herds, traits that can be measured on healthy pigs and that are genetically correlated with disease resilience, i.e. genetic indicator traits, offer a strategy to select for disease resilience. Our objective was to evaluate mitogen stimulation assays on peripheral blood mononuclear cells from young healthy pigs as genetic indicators for disease resilience. Data were from a natural disease challenge in which batches of 60 or 75 naïve Yorkshire x Landrace piglets were introduced every three weeks into a continuous flow barn that was seeded with multiple diseases. In this environment, disease resilience traits, including growth, treatment, and mortality rates, were recorded on 3136 pigs that were genotyped with a high-density marker panel. Peripheral blood mononuclear cells from 882 of these pigs from 19 batches were isolated from whole blood collected prior to the disease challenge and stimulated with five mitogens: concanavalin A (ConA), phytohemagglutinin (PHA), pokeweed mitogen (PWM), lipopolysaccharide (LPS), and phorbol myristate acetate (PMA). Proliferation of cells was evaluated at 48, 72, and 96 hrs and compared to unstimulated samples (rest count). Heritabilities of cell proliferation were estimated using a model with batch as a fixed effect, covariates of entry age, rest count, and complete blood count proportions of lymphocytes, monocytes, eosinophils, and basophils, and pen, litter, and animal genetics as random effects. Heritability estimates were highest for response to ConA (0.30+0.09, 0.28+0.10, 0.17+0.10, and 0.25+0.10 at 48, 72, and 96 hrs after stimulation and for area under the curve across the three time points, respectively). Estimates were in a similar range for response to PHA and PMA, but low for PWM and LPS. Responses to ConA, PHA, and PMA were moderately genetically correlated with several disease resilience traits and in the expected direction but individual estimates were not significantly different from zero due to large standard errors. In conclusion, although validation is needed, mitogen stimulation assays, in particular based on ConA, show promise as genetic indicator traits for disease resilience.
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http://dx.doi.org/10.1093/jas/skab084DOI Listing
May 2021

Heritability of perching behavior and its genetic relationship with incidence of floor eggs in Rhode Island Red chickens.

Genet Sel Evol 2021 Apr 21;53(1):38. Epub 2021 Apr 21.

Department of Animal Science, Iowa State University, 806 Stange Road, 239E Kildee Hall, Ames, IA, 50010, USA.

Background: As cage-free production systems become increasingly popular, behavioral traits such as nesting behavior and temperament have become more important. The objective of this study was to estimate heritabilities for frequency of perching and proportion of floor eggs and their genetic correlation in two Rhode Island Red lines.

Results: The percent of hens observed perching tended to increase and the proportion of eggs laid on the floor tended to decrease as the test progressed. This suggests the ability of hens to learn to use nests and perches. Under the bivariate repeatability model, estimates of heritability in the two lines were 0.22 ± 0.04 and 0.07 ± 0.05 for the percent of hens perching, and 0.52 ± 0.05 and 0.45 ± 0.05 for the percent of floor eggs. Estimates of the genetic correlation between perching and floor eggs were - 0.26 ± 0.14 and - 0.19 ± 0.27 for the two lines, suggesting that, genetically, there was some tendency for hens that better use perches to also use nests; but the phenotypic correlation was close to zero. Random regression models indicated the presence of a genetic component for learning ability.

Conclusions: In conclusion, perching and tendency to lay floor eggs were shown to be a learned behavior, which stresses the importance of proper management and training of pullets and young hens. A significant genetic component was found, confirming the possibility to improve nesting behavior for cage-free systems through genetic selection.
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http://dx.doi.org/10.1186/s12711-021-00630-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059289PMC
April 2021

Distinct transcriptomic response to Newcastle disease virus infection during heat stress in chicken tracheal epithelial tissue.

Sci Rep 2021 Apr 2;11(1):7450. Epub 2021 Apr 2.

Feed the Future Innovation Lab for Genomics to Improve Poultry, University of California, Davis, CA, 95616, USA.

Newcastle disease (ND) has a great impact on poultry health and welfare with its most virulent (velogenic) strain. In addition, issues exacerbated by the increase in global temperatures necessitates a greater understanding of the host immune response when facing a combination of biotic and abiotic stress factors in poultry production. Previous investigations have revealed that the host immune response is tissue-specific. The goal of this study was to identify genes and/or signaling pathways associated with immune response to NDV (Newcastle disease virus) in the trachea, an essential organ where NDV replicate after the infection, by profiling the tissue specific transcriptome response in two genetically distinct inbred chicken lines when exposed to both abiotic and biotic stressors. Fayoumis appear to be able to respond more effectively (lower viral titer, higher antibody levels, immune gene up-regulation) and earlier than Leghorns. Our results suggest NDV infection in Fayoumis appears to elicit proinflammatory processes, and pathways such as the inhibition of cell viability, cell proliferation of lymphocytes, and transactivation of RNA, more rapidly than in Leghorns. These differences in immune response converge at later timepoints which may indicate that Leghorns eventually regulate its immune response to infection. The profiling of the gene expression response in the trachea adds to our understanding of the chicken host response to NDV infection and heat stress on a whole genome level and provides potential candidate genes and signaling pathways for further investigation into the characterization of the time-specific and pathway specific responses in Fayoumis and Leghorns.
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http://dx.doi.org/10.1038/s41598-021-86795-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018950PMC
April 2021

Genomics of response to porcine reproductive and respiratory syndrome virus in purebred and crossbred sows: antibody response and performance following natural infection vs. vaccination.

J Anim Sci 2021 May;99(5)

Department of Animal Science, Iowa State University, Ames, IA 50011, USA.

Antibody response, measured as sample-to-positive (S/P) ratio, to porcine reproductive and respiratory syndrome virus (PRRSV) following a PRRSV-outbreak (S/POutbreak) in a purebred nucleus and following a PRRSV-vaccination (S/PVx) in commercial crossbred herds have been proposed as genetic indicator traits for improved reproductive performance in PRRSV-infected purebred and PRRSV-vaccinated crossbred sows, respectively. In this study, we investigated the genetic relationships of S/POutbreak and S/PVx with performance at the commercial (vaccinated crossbred sows) and nucleus level (non-infected and PRRSV-infected purebred sows), respectively, and tested the effect of previously identified SNP for these indicator traits. Antibody response was measured on 541 Landrace sows ~54 d after the start of a PRRSV outbreak, and on 906 F1 (Landrace × Large White) gilts ~50 d after vaccination with a commercial PRRSV vaccine. Reproductive performance was recorded for 711 and 428 Landrace sows before and during the PRRSV outbreak, respectively, and for 811 vaccinated F1 animals. The estimate of the genetic correlation (rg) of S/POutbreak with S/PVx was 0.72 ± 0.18. The estimates of rg of S/POutbreak with reproductive performance in vaccinated crossbred sows were low to moderate, ranging from 0.05 ± 0.23 to 0.30 ± 0.20. The estimate of rg of S/PVx with reproductive performance in non-infected purebred sows was moderate and favorable with number born alive (0.50 ± 0.23) but low (0 ± 0.23 to -0.11 ± 0.23) with piglet mortality traits. The estimates of rg of S/PVx were moderate and negative (-0.38 ± 0.21) with number of mummies in PRRSV-infected purebred sows and low with other traits (-0.30 ± 0.18 to 0.05 ± 0.18). Several significant associations (P0 > 0.90) of previously reported SNP for S/P ratio (ASGA0032063 and H3GA0020505) were identified for S/P ratio and performance in non-infected purebred and PRRSV-exposed purebred and crossbred sows. Genomic regions harboring the major histocompatibility complex class II region significantly contributed to the genetic correlation of antibody response to PRRSV with most of the traits analyzed. These results indicate that selection for antibody response in purebred sows following a PRRSV outbreak in the nucleus and for antibody response to PRRSV vaccination measured in commercial crossbred sows are expected to increase litter size in purebred and commercial sows.
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http://dx.doi.org/10.1093/jas/skab097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118356PMC
May 2021