4 results on '"G. Boink"'
Search Results
2. Comparative characterization of single cells and engineered heart tissues from hiPSC-derived cardiomyocyte subtypes
- Author
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J Li, A Wiesinger, L Fokkert, B Boukens, A Verkerk, V Christoffels, G Boink, and H Devalla
- Subjects
Physiology ,Physiology (medical) ,Cardiology and Cardiovascular Medicine - Abstract
Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Research council starting grant 714866 and associated proof-of-concept grant 899422 ZonMW and the Dutch Heart foundation MKMD grant 114021512 and Dutch Heart Foundation Dekker fellowship 2020T023 Rationale: Human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes represent an excellent in vitro platform to study cardiac development and model patient-specific diseases. However, their widespread application in drug discovery and regenerative approaches has not yet been realized at least in part due to limited comparative characterization of the available cardiomyocyte subtypes and lack of multicellular models that allow assessment of physiologically relevant parameters. Objective Perform comprehensive characterization of hiPSC-derived sinoatrial nodal cardiomyocytes (SANCM), atrial cardiomyocytes (ACM) and ventricular cardiomyocytes (VCM) from 2D and 3D cultures. Methods SANCM, ACM and VCM were generated using directed differentiation protocols. Electrophysiological analysis was performed by single cell patch-clamp. Subtype-specific differences were further characterized by response to neurohumoral agents noradrenaline, and carbachol and If blocker ivabradine. Next, we generated EHTs to evaluate the effect of 3D culturing on cardiomyocyte subtypes and performed optical mapping. To establish a model to study impulse initiation and propagation in vitro, we generated binary EHTs (BIN-EHTs) composed of heteropolar ends of SANCM and ACM. Results Gene expression analysis and single cell electrophysiology confirmed identities of respective cardiomyocyte subtypes. While response to noradrenaline and carbachol were as expected, ivabradine testing showed the functional presence of pacemaker current If in ACM, besides SANCM. After three weeks in culture as EHTs, cardiac structural genes were markedly upregulated in all groups. Optical mapping demonstrated a three-fold increase in conduction velocities in ACM and VCM while SANCM EHTs retained slower conduction velocities recapitulating in vivo differences. In BIN-EHTs, SANCM end of the EHT consistently paced the tissues under baseline conditions. Upon treatment with ivabradine, cycle length of BIN-EHTs increased and impulse initiation switched to ACM end in the majority of tissues. Conclusions We performed comprehensive characterization of hiPSC-cardiomyocyte subtypes, which recapitulated salient features of their in vivo counterparts. BIN-EHT constructs composed of SANCM and ACM are a valuable rudimentary model for investigating impulse formation and propagation in vitro.
- Published
- 2022
3. Geographical contrasts of Y-chromosomal haplogroups from wild and domestic goats reveal ancient migrations and recent introgressions.
- Author
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Nijman IJ, Rosen BD, Bardou P, Faraut T, Cumer T, Daly KG, Zheng Z, Cai Y, Asadollahpour H, Kul BÇ, Zhang WY, E G, Ayin A, Baird H, Bakhtin M, Bâlteanu VA, Barfield D, Berger B, Blichfeldt T, Boink G, Bugiwati SRA, Cai Z, Carolan S, Clark E, Cubric-Curik V, Dagong MIA, Dorji T, Drew L, Guo J, Hallsson J, Horvat S, Kantanen J, Kawaguchi F, Kazymbet P, Khayatzadeh N, Kim N, Shah MK, Liao Y, Martínez A, Masangkay JS, Masaoka M, Mazza R, McEwan J, Milanesi M, Omar FM, Nomura Y, Ouchene-Khelifi NA, Pereira F, Sahana G, Salavati M, Sasazaki S, Da Silva A, Simčič M, Sölkner J, Sutherland A, Tigchelaar J, Zhang H, Ajmone-Marsan P, Bradley DG, Colli L, Drögemüller C, Jiang Y, Lei C, Mannen H, Pompanon F, Tosser-Klopp G, and Lenstra JA
- Subjects
- Animals, Goats genetics, Haplotypes genetics, Phylogeny, Y Chromosome genetics, DNA, Mitochondrial genetics, Genetic Variation
- Abstract
By their paternal transmission, Y-chromosomal haplotypes are sensitive markers of population history and male-mediated introgression. Previous studies identified biallelic single-nucleotide variants in the SRY, ZFY and DDX3Y genes, which in domestic goats identified four major Y-chromosomal haplotypes, Y1A, Y1B, Y2A and Y2B, with a marked geographical partitioning. Here, we extracted goat Y-chromosomal variants from whole-genome sequences of 386 domestic goats (75 breeds) and seven wild goat species, which were generated by the VarGoats goat genome project. Phylogenetic analyses indicated domestic haplogroups corresponding to Y1B, Y2A and Y2B, respectively, whereas Y1A is split into Y1AA and Y1AB. All five haplogroups were detected in 26 ancient DNA samples from southeast Europe or Asia. Haplotypes from present-day bezoars are not shared with domestic goats and are attached to deep nodes of the trees and networks. Haplogroup distributions for 186 domestic breeds indicate ancient paternal population bottlenecks and expansions during migrations into northern Europe, eastern and southern Asia, and Africa south of the Sahara. In addition, sharing of haplogroups indicates male-mediated introgressions, most notably an early gene flow from Asian goats into Madagascar and the crossbreeding that in the 19th century resulted in the popular Boer and Anglo-Nubian breeds. More recent introgressions are those from European goats into the native Korean goat population and from Boer goat into Uganda, Kenya, Tanzania, Malawi and Zimbabwe. This study illustrates the power of the Y-chromosomal variants for reconstructing the history of domestic species with a wide geographical range., (© 2022 The Authors. Molecular Ecology published by John Wiley & Sons Ltd.)
- Published
- 2022
- Full Text
- View/download PDF
4. Patterns of homozygosity in insular and continental goat breeds.
- Author
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Cardoso TF, Amills M, Bertolini F, Rothschild M, Marras G, Boink G, Jordana J, Capote J, Carolan S, Hallsson JH, Kantanen J, Pons A, and Lenstra JA
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- Animals, Europe, Genetic Variation, Genetics, Population, Genomics methods, Genotype, Iceland, Ireland, Madagascar, Mediterranean Islands, Morocco, Population Density, Zimbabwe, Breeding methods, Goats genetics, Homozygote, Polymorphism, Single Nucleotide
- Abstract
Background: Genetic isolation of breeds may result in a significant loss of diversity and have consequences on health and performance. In this study, we examined the effect of geographic isolation on caprine genetic diversity patterns by genotyping 480 individuals from 25 European and African breeds with the Goat SNP50 BeadChip and comparing patterns of homozygosity of insular and nearby continental breeds., Results: Among the breeds analysed, number and total length of ROH varied considerably and depending on breeds, ROH could cover a substantial fraction of the genome (up to 1.6 Gb in Icelandic goats). When compared with their continental counterparts, goats from Iceland, Madagascar, La Palma and Ireland (Bilberry and Arran) displayed a significant increase in ROH coverage, ROH number and F
ROH values (P value < 0.05). Goats from Mediterranean islands represent a more complex case because certain populations displayed a significantly increased level of homozygosity (e.g. Girgentana) and others did not (e.g. Corse and Sarda). Correlations of number and total length of ROH for insular goat populations with the distance between islands and the nearest continental locations revealed an effect of extremely long distances on the patterns of homozygosity., Conclusions: These results indicate that the effects of insularization on the patterns of homozygosity are variable. Goats raised in Madagascar, Iceland, Ireland (Bilberry and Arran) and La Palma, show high levels of homozygosity, whereas those bred in Mediterranean islands display patterns of homozygosity that are similar to those found in continental populations. These results indicate that the diversity of insular goat populations is modulated by multiple factors such as geographic distribution, population size, demographic history, trading and breed management.- Published
- 2018
- Full Text
- View/download PDF
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