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Your search keyword '"Hun, Michael L."' showing total 12 results
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12 results on '"Hun, Michael L."'

1. The activity of early-life gene regulatory elements is hijacked in aging through pervasive AP-1-linked chromatin opening

Author

Patrick, Ralph, Naval-Sanchez, Marina, Deshpande, Nikita, Huang, Yifei, Zhang, Jingyu, Chen, Xiaoli, Yang, Ying, Tiwari, Kanupriya, Esmaeili, Mohammadhossein, Tran, Minh, Mohamed, Amin R., Wang, Binxu, Xia, Di, Ma, Jun, Bayliss, Jacqueline, Wong, Kahlia, Hun, Michael L., Sun, Xuan, Cao, Benjamin, Cottle, Denny L., Catterall, Tara, Barzilai-Tutsch, Hila, Troskie, Robin-Lee, Chen, Zhian, Wise, Andrea F., Saini, Sheetal, Soe, Ye Mon, Kumari, Snehlata, Sweet, Matthew J., Thomas, Helen E., Smyth, Ian M., Fletcher, Anne L., Knoblich, Konstantin, Watt, Matthew J., Alhomrani, Majid, Alsanie, Walaa, Quinn, Kylie M., Merson, Tobias D., Chidgey, Ann P., Ricardo, Sharon D., Yu, Di, Jardé, Thierry, Cheetham, Seth W., Marcelle, Christophe, Nilsson, Susan K., Nguyen, Quan, White, Melanie D., and Nefzger, Christian M.

Published
2024
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8. Gelatin-Based 3D Microgels for In Vitro T Lineage Cell Generation

Author

Suraiya, Anisha B., Hun, Michael L., Truong, Vinh X., Forsythe, John S., and Chidgey, Ann P.

Abstract

T cells are predominantly produced by the thymus and play a significant role in maintaining our adaptive immune system. Physiological involution of the thymus occurs gradually with age, compromising naive T cell output, which can have severe clinical complications. Also, T cells are utilized as therapeutic agents in cancer immunotherapies. Therefore, there is an increasing need for strategies aimed at generating naive T cells. The majority of in vitro T cell generation studies are performed in two-dimensional (2D) cultures, which ignore the physiological thymic microenvironment and are not scalable; therefore, we applied a new three-dimensional (3D) approach. Here, we use a gelatin-based 3D microgel system for T lineage induction by co-culturing OP9-DL4 cells and mouse fetal-liver-derived hematopoietic stem cells (HSCs). Flow cytometric analysis revealed that microgel co-cultures supported T lineage induction similar to 2D cultures while providing a 3D environment. We also encapsulated mouse embryonic thymic epithelial cells (TECs) within the microgels to provide a defined 3D culture platform. The microgel system supported TEC maintenance and retained their phenotype. Together, these data show that our microgel system has the capacity for TEC maintenance and induction of in vitro T lineage differentiation with potential for scalability.

Published
2024
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10. A novel Foxn1eGFP/+ mouse model identifies Bmp4-induced maintenance of Foxn1 expression and thymic epithelial progenitor populations.

Author

Barsanti, Marco, Lim, Joanna M. C., Hun, Michael L., Lister, Natalie, Wong, Kahlia, Hammett, Maree V., Lepletier, Ailin, Boyd, Richard L., Giudice, Antonietta, and Chidgey, Ann P.

Abstract

Although forkhead-box n1 (Foxn1) is a critical thymic epithelial cell regulator in thymus organogenesis, its association with epithelial differentiation and homeostasis in the postnatal and aged thymic microenvironment remains conflicting. Consequently, we have generated a Foxn1eGFP/+ knock-in mouse model that allows for refined investigation of the aging thymic epithelium. This reporter line differs from those previously published in that concomitant expression of enhanced green fluorescent protein enables live cell sorting of Foxn1+ cell populations. Our heterozygotes did not exhibit haploinsufficiency, with Foxn1 expression resembling that of wild-type mice. Comparative analysis between Foxn1 and enhanced green fluorescent protein at both the transcriptional and translational levels revealed co-localization, with progressive down-regulation observed predominantly in the aging cortical epithelium. Supplementation with bone morphogenetic protein (Bmp)-4 enhanced Foxn1 expression and colony forming efficiency in both embryonic and adult progenitor 3D cultures. Strikingly, selective maintenance of immature cortical and medullary epithelial cells was observed which is consistent with the higher Bmp receptor 2 expression levels seen in these progenitor populations. This study demonstrates the significance of our mouse model in unraveling the role of this master regulator in thymus development, homeostasis and aging, providing a faithful reporter system for phenotypic and functional investigations. [ABSTRACT FROM AUTHOR]

Published
2017
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11. In situ-forming click-crosslinked gelatin based hydrogels for 3D culture of thymic epithelial cellsElectronic supplementary information (ESI) available. See DOI: 10.1039/c6bm00254d

Author

TruongThese authors contributed equally., Vinh X., Hun, Michael L., Li, Fanyi, Chidgey, Ann P., and Forsythe, John S.

Abstract

Hydrogels prepared from naturally derived gelatin can provide a suitable environment for cell attachment and growth, making them favourable materials in tissue engineering. However, physically crosslinked gelatin hydrogels are not stable under physiological conditions while chemical crosslinking of gelatin by radical polymerization may be harmful to cells. In this study, we attached the norbornene functional group to gelatin, which was subsequently crosslinked with a polyethylene glycol (PEG) linker viathe nitrile oxide-norbornene click reaction. The rapid crosslinking process allows the hydrogel to be formed within minutes of mixing the polymer solutions under physiological conditions, allowing the gels to be used as injectable materials. The hydrogels properties including mechanical strength, swelling and degradation, can be tuned by changing either the ratio of the reacting groups or the total concentration of the polymer precursors. Murine embryonic fibroblastic cells cultured in soft gels (2 wt% of gelatin and 1 wt% of PEG linker) demonstrated high cell viability as well as similar phenotypic profiles (PDGFRα and MTS15) to Matrigel cultures over 5 days. Thymic epithelial cell and fibroblast co-cultures produced epithelial colonies in these gels following 7 days incubation. These studies demonstrate that gelatin based hydrogels, prepared using “click” crosslinking, provide a robust cell culture platform with retained benefits of the gelatin material, and are therefore suitable for use in various tissue engineering applications.

Published
2016
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12. A novel Foxn1 eGFP/+ mouse model identifies Bmp4-induced maintenance of Foxn1 expression and thymic epithelial progenitor populations.

Author

Barsanti M, Lim JM, Hun ML, Lister N, Wong K, Hammett MV, Lepletier A, Boyd RL, Giudice A, and Chidgey AP

Subjects
Animals, Bone Morphogenetic Protein 4 metabolism, Bone Morphogenetic Protein Receptors, Type II genetics, Bone Morphogenetic Protein Receptors, Type II metabolism, Cells, Cultured, Forkhead Transcription Factors genetics, Gene Expression Regulation, Green Fluorescent Proteins genetics, Homeostasis, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Transgenic, Models, Animal, Thymus Gland cytology, Aging physiology, Epithelial Cells physiology, Forkhead Transcription Factors metabolism, Stem Cells physiology, Thymus Gland physiology
Abstract

Although forkhead-box n1 (Foxn1) is a critical thymic epithelial cell regulator in thymus organogenesis, its association with epithelial differentiation and homeostasis in the postnatal and aged thymic microenvironment remains conflicting. Consequently, we have generated a Foxn1 eGFP/+ knock-in mouse model that allows for refined investigation of the aging thymic epithelium. This reporter line differs from those previously published in that concomitant expression of enhanced green fluorescent protein enables live cell sorting of Foxn1 + cell populations. Our heterozygotes did not exhibit haploinsufficiency, with Foxn1 expression resembling that of wild-type mice. Comparative analysis between Foxn1 and enhanced green fluorescent protein at both the transcriptional and translational levels revealed co-localization, with progressive down-regulation observed predominantly in the aging cortical epithelium. Supplementation with bone morphogenetic protein (Bmp)-4 enhanced Foxn1 expression and colony forming efficiency in both embryonic and adult progenitor 3D cultures. Strikingly, selective maintenance of immature cortical and medullary epithelial cells was observed which is consistent with the higher Bmp receptor 2 expression levels seen in these progenitor populations. This study demonstrates the significance of our mouse model in unraveling the role of this master regulator in thymus development, homeostasis and aging, providing a faithful reporter system for phenotypic and functional investigations., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Published
2017
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