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455 results on '"Niemann, Heiner"'

3. Stem cell-derived porcine macrophages as a new platform for studying host-pathogen interactions

Author

Meek, Stephen, Watson, Tom, Eory, Lel, McFarlane, Gus, Wynne, Felicity J., McCleary, Stephen, Dunn, Laura E. M., Charlton, Emily M., Craig, Chloe, Shih, Barbara, Regan, Tim, Taylor, Ryan, Sutherland, Linda, Gossner, Anton, Chintoan-Uta, Cosmin, Fletcher, Sarah, Beard, Philippa M., Hassan, Musa A., Grey, Finn, Hope, Jayne C., Stevens, Mark P., Nowak-Imialek, Monika, Niemann, Heiner, Ross, Pablo J., Tait-Burkard, Christine, Brown, Sarah M., Lefevre, Lucas, Thomson, Gerard, McColl, Barry W., Lawrence, Alistair B., Archibald, Alan L., Steinbach, Falko, Crooke, Helen R., Gao, Xuefei, Liu, Pentao, and Burdon, Tom

Published
2022
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7. Establishment of porcine and human expanded potential stem cells

Author

Gao, Xuefei, Nowak-Imialek, Monika, Chen, Xi, Chen, Dongsheng, Herrmann, Doris, Ruan, Degong, Chen, Andy Chun Hang, Eckersley-Maslin, Melanie A., Ahmad, Shakil, Lee, Yin Lau, Kobayashi, Toshihiro, Ryan, David, Zhong, Jixing, Zhu, Jiacheng, Wu, Jian, Lan, Guocheng, Petkov, Stoyan, Yang, Jian, Antunes, Liliana, Campos, Lia S., Fu, Beiyuan, Wang, Shengpeng, Yong, Yu, Wang, Xiaomin, Xue, Song-Guo, Ge, Liangpeng, Liu, Zuohua, Huang, Yong, Nie, Tao, Li, Peng, Wu, Donghai, Pei, Duanqing, Zhang, Yi, Lu, Liming, Yang, Fengtang, Kimber, Susan J., Reik, Wolf, Zou, Xiangang, Shang, Zhouchun, Lai, Liangxue, Surani, Azim, Tam, Patrick P. L., Ahmed, Asif, Yeung, William Shu Biu, Teichmann, Sarah A., Niemann, Heiner, and Liu, Pentao

Published
2019
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14. Genetic knockout of porcine GGTA1 or CMAH/GGTA1 is associated with the emergence of neo‐glycans.

Author

Morticelli, Lucrezia, Rossdam, Charlotte, Cajic, Samanta, Böthig, Dietmar, Magdei, Mikhail, Tuladhar, Sugat Ratna, Petersen, Björn, Fischer, Konrad, Rapp, Erdmann, Korossis, Sotirios, Haverich, Axel, Schnieke, Angelika, Niemann, Heiner, Buettner, Falk F. R., and Hilfiker, Andres

Subjects
GLYCANS, CAPILLARY electrophoresis, ORGANS (Anatomy), LASER-induced fluorescence, TRANSPLANTATION of organs, tissues, etc.
Abstract

Background: Pig‐derived tissues could overcome the shortage of human donor organs in transplantation. However, the glycans with terminal α‐Gal and Neu5Gc, which are synthesized by enzymes, encoded by the genes GGTA1 and CMAH, are known to play a major role in immunogenicity of porcine tissue, ultimately leading to xenograft rejection. Methods: The N‐glycome and glycosphingolipidome of native and decellularized porcine pericardia from wildtype (WT), GGTA1‐KO and GGTA1/CMAH‐KO pigs were analyzed by multiplexed capillary gel electrophoresis coupled to laser‐induced fluorescence detection. Results: We identified biantennary and core‐fucosylated N‐glycans terminating with immunogenic α‐Gal‐ and α‐Gal‐/Neu5Gc‐epitopes on pericardium of WT pigs that were absent in GGTA1 and GGTA1/CMAH‐KO pigs, respectively. Levels of N‐glycans terminating with galactose bound in β(1‐4)‐linkage to N‐acetylglucosamine and their derivatives elongated by Neu5Ac were increased in both KO groups. N‐glycans capped with Neu5Gc were increased in GGTA1‐KO pigs compared to WT, but were not detected in GGTA1/CMAH‐KO pigs. Similarly, the ganglioside Neu5Gc‐GM3 was found in WT and GGTA1‐KO but not in GGTA1/CMAH‐KO pigs. The applied detergent based decellularization efficiently removed GSL glycans. Conclusion: Genetic deletion of GGTA1 or GGTA1/CMAH removes specific epitopes providing a more human‐like glycosylation pattern, but at the same time changes distribution and levels of other porcine glycans that are potentially immunogenic. [ABSTRACT FROM AUTHOR]

Published
2023
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22. Stem cell-derived macrophages as a new platform for studying host-pathogen interactions in livestock

Author

Meek, Stephen, Watson, Tom, Eory, Lel, McFarlane, Gus, Wynne, Felicity J., McCleary, Stephen, Dunn, Laura E.M., Charlton, Emily, Criag, Chloe, Shih, Barbara, Regan, Tim, Taylor, Ryan, Sutherland, Linda, Gossner, Anton, Chintoan-Uta, Cosmin, Fletcher, Sarah, Beard, Pip, Hassan, Musa, Grey, Finn, Hope, Jayne, Stevens, Mark, Nowak-Imialek, Monika, Niemann, Heiner, Ross, Pablo J., Tait-Burkard, Christine, Brown, Sarah, Lefevre, Lucas, Thomson, Gerard, McColl, Barry W, Lawrence, A B, Archibald, Alan, Steinbach, Falko, Crooke , Helen R., Gao, Xuefei, Liu, Pentao, and Burdon, Tom

Abstract

Infectious diseases of farmed and wild animals pose a recurrent threat to food security and human health. The macrophage, a key component of the innate immune system, is the first line of defence against many infectious agents and plays a major role in shaping the adaptive immune response. However, this phagocyte is a target and host for many pathogens. Understanding the molecular basis of interactions between macrophages and pathogens is therefore crucial for the development of effective strategies to combat important infectious diseases. We explored how pluripotent stem cells (PSCs) can provide a limitless in vitro supply of genetically and experimentally tractable macrophages from livestock. Porcine and bovine PSC-derived macrophages (PSCdMs) exhibited molecular and functional characteristics of ex vivo primary macrophages. Pig PSCdMs were productively infected by Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) and African Swine Fever Virus (ASFV), two of the most economically important and devastating viruses in pig farming. Moreover, Pig PSCdMs were readily amenable to genetic modification by CRISPR/Cas9 gene editing applied in parental stem cells, or directly by lentiviral vector transduction. PSCs and differentiated derivatives therefore provide a useful and ethical experimental platform to investigate the genetic and molecular basis of host-pathogen interactions in livestock.

Published
2022
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48. The knockout of the HMG-Box Domain of the porcine SRY-gene by CRISPR/Cas RNP microinjection causes sex reversal in gene-edited pigs

Author

Kurtz, Stefanie, Frenzel, Antje, Lucas-Hahn, Andrea, Hassel, Petra, Becker, Roswitha, Ziegler, Maren, Nowak-Imialek, Monika, Schlegelberger, Brigitte, Göhring, Gudrun, Niemann, Heiner, and Petersen, Björn

Abstract

The sex-determining region on Y chromosome (SRY) is presumed as a main genetic switch of male sex development. Mutations within the SRY gene are associated with a male-to-female sex reversal syndrome in humans and other mammalian species such as mice and rabbits. However, the underlying mechanism causing this syndrome is not definitely known. To understand the genetic pathway of SRY, the investigation and analysis of morphological changes are essential. For the first time, we successfully generated a knockout of the SRY gene in pigs using microinjection of two Clustered regularly interspaced short palindromic repeats (CRISPR) – associated protein - 9 nuclease (Cas9) ribonucleoprotein (RNP) complexes targeting the centrally located “high mobility group”-box domain (HMG) of the SRY gene. Mutation within the porcine HMG-box domain resulted in the development of complete external and internal female genitalia in genetically male piglets. Uteri and oviducts displayed equal morphology compared to female wildtype controls, only the ovaries showed smaller size in sex reversal piglets. In contrast to the HMG-box domain deletion, a deletion within the 5’ flanking region of the HMG domain was not associated with sex reversal. In summary, this study demonstrates for the first time the main role of the HMG-box domain of the SRY gene triggering the male sex determination in pigs.

Published
2019
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