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Article ; Online: Developing standards to support cell technology applications.

Cao, Jiani / Stacey, Glyn / Shyh-Chang, Ng / Zhao, Tongbiao

2022 Volume 55, Issue 4, Page(s) e13210

MeSH term(s)	Technology
Language	English
Publishing date	2022-03-11
Publishing country	England
Document type	Letter
ZDB-ID	1064202-x
ISSN	1365-2184 ; 0008-8730 ; 0960-7722
ISSN (online)	1365-2184
ISSN	0008-8730 ; 0960-7722
DOI	10.1111/cpr.13210
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: A novel inducible haematopoietic cell-depleting mouse model for chimeric complementation of blood cells.

Cao, Weiyun / Cao, Jiani / Li, Xing / Xu, Haoyu / Tian, Jiayi / Li, Xiaoyan / Wang, Fengchao / Zhao, Tongbiao

Cell proliferation

2023 Volume 56, Issue 5, Page(s) e13472

Abstract: Haematopoietic stem cell transplantation (HSCT) is widely used in regenerative medicine. HSCT can be used not only to treat certain types of blood cancer and immune disorders but also to induce immune tolerance in organ transplantation. However, the ... ...

Abstract	Haematopoietic stem cell transplantation (HSCT) is widely used in regenerative medicine. HSCT can be used not only to treat certain types of blood cancer and immune disorders but also to induce immune tolerance in organ transplantation. However, the inadequacy of HSCs available for transplantation is still a major hurdle for clinical applications. Here, we established a novel inducible haematopoietic cell-depleting mouse model and tested the feasibility of using chimeric complementation to regenerate HSCs and their progeny cells. Large populations of syngeneic and major histocompatibility-mismatched haematopoietic cells were successfully regenerated by this model. The stable allogeneic chimeric mice maintained a substantial population of donor HSCs and Tregs, which indicated that the donor allogeneic HSCs successfully repopulated the recipient blood system, and the regenerated donor Tregs played essential roles in establishing immune tolerance in the allogeneic recipients. In addition, rat blood cells were detected in this model after xenotransplantation of rat whole bone marrow (BM) or Lin
MeSH term(s)	Humans ; Mice ; Rats ; Animals ; Hematopoietic Stem Cell Transplantation ; Bone Marrow Transplantation ; Hematopoietic Stem Cells ; Bone Marrow Cells ; Blood Cells ; Disease Models, Animal ; Mice, Inbred C57BL
Language	English
Publishing date	2023-05-17
Publishing country	England
Document type	Journal Article
ZDB-ID	1064202-x
ISSN	1365-2184 ; 0008-8730 ; 0960-7722
ISSN (online)	1365-2184
ISSN	0008-8730 ; 0960-7722
DOI	10.1111/cpr.13472
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

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Article: Autophagy in Normal Stem Cells and Specialized Cells.

Liu, Kun / Wang, Liang / Zhao, Tongbiao

Advances in experimental medicine and biology

2019 Volume 1206, Page(s) 489–508

Abstract: Autophagy, the intracellular degradation and dynamic recycling system, plays critical roles in pluripotent and differentiated cells. It protects the homeostasis of the intracellular environment and maintains the functions of cells by degrading and ... ...

Abstract	Autophagy, the intracellular degradation and dynamic recycling system, plays critical roles in pluripotent and differentiated cells. It protects the homeostasis of the intracellular environment and maintains the functions of cells by degrading and recycling cytoplasmic components. Autophagy is associated with the entire life cycle of the body, from the totipotent fertilized egg to the terminally differentiated cell. However, autophagy also plays distinct roles in these different life stages and in specific cell types. Here, we summarize the functions of autophagy in normal stem cells and in specialized cells.
MeSH term(s)	Aging ; Animals ; Autophagy ; Cell Differentiation ; Homeostasis ; Stem Cells/cytology
Language	English
Publishing date	2019-11-27
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/978-981-15-0602-4_23
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Article ; Online: Cellular metabolism and homeostasis in pluripotency regulation.

Liu, Kun / Cao, Jiani / Shi, Xingxing / Wang, Liang / Zhao, Tongbiao

Protein & cell

2020 Volume 11, Issue 9, Page(s) 630–640

Abstract: Pluripotent stem cells (PSCs) can immortally self-renew in culture with a high proliferation rate, and they possess unique metabolic characteristics that facilitate pluripotency regulation. Here, we review recent progress in understanding the mechanisms ... ...

Abstract	Pluripotent stem cells (PSCs) can immortally self-renew in culture with a high proliferation rate, and they possess unique metabolic characteristics that facilitate pluripotency regulation. Here, we review recent progress in understanding the mechanisms that link cellular metabolism and homeostasis to pluripotency regulation, with particular emphasis on pathways involving amino acid metabolism, lipid metabolism, the ubiquitin-proteasome system and autophagy. Metabolism of amino acids and lipids is tightly coupled to epigenetic modification, organelle remodeling and cell signaling pathways for pluripotency regulation. PSCs harness enhanced proteasome and autophagy activity to meet the material and energy requirements for cellular homeostasis. These regulatory events reflect a fine balance between the intrinsic cellular requirements and the extrinsic environment. A more complete understanding of this balance will pave new ways to manipulate PSC fate.
MeSH term(s)	Amino Acids ; Animals ; Autophagy ; Cell Differentiation ; Energy Metabolism ; Epigenesis, Genetic ; Humans ; Lipid Metabolism ; Pluripotent Stem Cells/cytology ; Pluripotent Stem Cells/metabolism ; Proteasome Endopeptidase Complex/metabolism ; Ubiquitin/metabolism
Chemical Substances	Amino Acids ; Ubiquitin ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
Language	English
Publishing date	2020-07-08
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2543451-2
ISSN	1674-8018 ; 1674-800X
ISSN (online)	1674-8018
ISSN	1674-800X
DOI	10.1007/s13238-020-00755-1
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The physiological roles of autophagy in the mammalian life cycle.

Wang, Liang / Ye, Xiongjun / Zhao, Tongbiao

Biological reviews of the Cambridge Philosophical Society

2018 Volume 94, Issue 2, Page(s) 503–516

Abstract: Autophagy is primarily an efficient intracellular catabolic pathway used for degradation of abnormal cellular protein aggregates and damaged organelles. Although autophagy was initially proposed to be a cellular stress responder, increasing evidence ... ...

Abstract	Autophagy is primarily an efficient intracellular catabolic pathway used for degradation of abnormal cellular protein aggregates and damaged organelles. Although autophagy was initially proposed to be a cellular stress responder, increasing evidence suggests that it carries out normal physiological roles in multiple biological processes. To date, autophagy has been identified in most organs and at many different developmental stages, indicating that it is not only essential for cellular homeostasis and renovation, but is also important for organ development. Herein, we summarize our current understanding of the functions of autophagy (which here refers to macroautophagy) in the mammalian life cycle.
MeSH term(s)	Animals ; Autophagosomes/metabolism ; Autophagy/genetics ; Autophagy/physiology ; Life Cycle Stages/genetics ; Life Cycle Stages/physiology ; Lysosomes/metabolism ; Mammals/embryology ; Mammals/genetics ; Mammals/growth & development ; Mammals/physiology ; Stem Cells/physiology
Language	English
Publishing date	2018-09-21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1423558-4
ISSN	1469-185X ; 0006-3231 ; 1464-7931
ISSN (online)	1469-185X
ISSN	0006-3231 ; 1464-7931
DOI	10.1111/brv.12464
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Suppression of flavivirus transmission from animal hosts to mosquitoes with a mosquito-delivered vaccine.

Wen, Dan / Ding, Limin S / Zhang, Yanan / Li, Xiaoye / Zhang, Xing / Yuan, Fei / Zhao, Tongbiao / Zheng, Aihua

Nature communications

2022 Volume 13, Issue 1, Page(s) 7780

Abstract: Zoonotic viruses circulate in the natural reservoir and sporadically spill over into human populations, resulting in endemics or pandemics. We previously found that the Chaoyang virus (CYV), an insect-specific flavivirus (ISF), is replication-defective ... ...

Abstract	Zoonotic viruses circulate in the natural reservoir and sporadically spill over into human populations, resulting in endemics or pandemics. We previously found that the Chaoyang virus (CYV), an insect-specific flavivirus (ISF), is replication-defective in vertebrate cells. Here, we develope a proof-of-concept mosquito-delivered vaccine to control the Zika virus (ZIKV) within inaccessible wildlife hosts using CYV as the vector. The vaccine is constructed by replacing the pre-membrane and envelope (prME) proteins of CYV with those of ZIKV, assigned as CYV-ZIKV. CYV-ZIKV replicates efficiently in Aedes mosquitoes and disseminates to the saliva, with no venereal or transovarial transmission observed. To reduce the risk of CYV-ZIKV leaking into the environment, mosquitoes are X-ray irradiated to ensure 100% infertility, which does not affect the titer of CYV-ZIKV in the saliva. Immunization of mice via CYV-ZIKV-carrying mosquito bites elicites robust and persistent ZIKV-specific immune responses and confers complete protection against ZIKV challenge. Correspondingly, the immunized mice could no longer transmit the challenged ZIKV to naïve mosquitoes. Therefore, immunization with an ISF-vectored vaccine via mosquito bites is feasible to induce herd immunity in wildlife hosts of ZIKV. Our study provides a future avenue for developing a mosquito-delivered vaccine to eliminate zoonotic viruses in the sylvatic cycle.
Language	English
Publishing date	2022-12-16
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-35407-x
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: BNIP3-dependent mitophagy safeguards ESC genomic integrity via preventing oxidative stress-induced DNA damage and protecting homologous recombination.

Zhao, Qian / Liu, Kun / Zhang, Lin / Li, Zheng / Wang, Liang / Cao, Jiani / Xu, Youqing / Zheng, Aihua / Chen, Quan / Zhao, Tongbiao

Cell death & disease

2022 Volume 13, Issue 11, Page(s) 976

Abstract: Embryonic stem cells (ESCs) have a significantly lower mutation load compared to somatic cells, but the mechanisms that guard genomic integrity in ESCs remain largely unknown. Here we show that BNIP3-dependent mitophagy protects genomic integrity in ... ...

Abstract	Embryonic stem cells (ESCs) have a significantly lower mutation load compared to somatic cells, but the mechanisms that guard genomic integrity in ESCs remain largely unknown. Here we show that BNIP3-dependent mitophagy protects genomic integrity in mouse ESCs. Deletion of Bnip3 increases cellular reactive oxygen species (ROS) and decreases ATP generation. Increased ROS in Bnip3
MeSH term(s)	Mice ; Animals ; Mitophagy/genetics ; Reactive Oxygen Species/metabolism ; AMP-Activated Protein Kinases/metabolism ; Oxidative Stress ; Genomics ; Homologous Recombination ; DNA Damage/genetics ; Adenosine Triphosphate/metabolism ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Mitochondrial Proteins/genetics ; Mitochondrial Proteins/metabolism
Chemical Substances	Reactive Oxygen Species ; AMP-Activated Protein Kinases (EC 2.7.11.31) ; Adenosine Triphosphate (8L70Q75FXE) ; BNip3 protein, mouse ; Membrane Proteins ; Mitochondrial Proteins
Language	English
Publishing date	2022-11-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2541626-1
ISSN	2041-4889 ; 2041-4889
ISSN (online)	2041-4889
ISSN	2041-4889
DOI	10.1038/s41419-022-05413-4
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Evaluating mitophagy in embryonic stem cells by using fluorescence-based imaging.

Liu, Kun / Li, Xing / Li, Zheng / Cao, Jiani / Li, Xiaoyan / Xu, Youqing / Liu, Lei / Zhao, Tongbiao

Frontiers in cell and developmental biology

2022 Volume 10, Page(s) 910464

Abstract: Embryonic stem cells (ESCs), which are characterized by the capacity for self-renewal and pluripotency, hold great promise for regenerative medicine. Increasing evidence points to the essential role of mitophagy in pluripotency regulation. Our recent ... ...

Abstract	Embryonic stem cells (ESCs), which are characterized by the capacity for self-renewal and pluripotency, hold great promise for regenerative medicine. Increasing evidence points to the essential role of mitophagy in pluripotency regulation. Our recent work showed that PINK1/OPTN take part in guarding ESC mitochondrial homeostasis and pluripotency. Evaluating mitophagy in ESCs is important for exploring the relationships between mitochondrial homeostasis and pluripotency. ESCs are smaller in size than adult somatic cells and the mitophagosomes in ESCs are difficult to observe. Many methods have been employed-for example, detecting colocalization of LC3-II and mitochondria-to evaluate mitophagy in ESCs. However, it is important to define an objective way to detect mitophagy in ESCs. Here, we evaluated two commonly used fluorescence-based imaging methods to detect mitophagy in ESCs. By using autophagy- or mitophagy-defective ESC lines, we showed that the mito-Keima (mt-Keima) system is a suitable and effective way for detecting and quantifying mitophagy in ESCs. Our study provides evidence that mt-Keima is an effective tool to study mitophagy function in ESCs.
Language	English
Publishing date	2022-09-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2022.910464
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Article ; Online: IL-21R-STAT3 signalling initiates a differentiation program in uterine tissue-resident NK cells to support pregnancy.

Han, Mengwei / Hu, Luni / Wu, Di / Zhang, Yime / Li, Peng / Zhao, Xingyu / Zeng, Yanyu / Ren, Guanqun / Hou, Zhiyuan / Pang, Yanli / Zhao, Tongbiao / Zhong, Chao

Nature communications

2023 Volume 14, Issue 1, Page(s) 7109

Abstract: Tissue-resident Natural Killer (trNK) cells are crucial components of local immunity that activate rapidly upon infection. However, under steady state conditions, their responses are tightly controlled to prevent unwanted tissue damage. The mechanisms ... ...

Abstract	Tissue-resident Natural Killer (trNK) cells are crucial components of local immunity that activate rapidly upon infection. However, under steady state conditions, their responses are tightly controlled to prevent unwanted tissue damage. The mechanisms governing their differentiation and activation are not fully understood. Here, we characterise uterine trNK cells longitudinally during pregnancy by single cell RNA sequencing and find that the combined expression pattern of 4-1BB and CD55 defines their three distinct stages of differentiation in mice. Mechanistically, an IL-21R-STAT3 axis is essential for initiating the trNK cell differentiation. The fully differentiated trNK cells demonstrate enhanced functionality, which is necessary for remodelling spiral arteries in the decidua. We identify an apoptotic program that is specific to the terminal differentiation stage, which may preclude tissue damage by these highly activated trNK cells. In summary, uterine trNK cells become intensely active and effective during pregnancy, but tightly controlled via a differentiation program that also limits potential harm, suggesting an intricate mechanism for harnessing trNK cells in maintaining pregnancy.
MeSH term(s)	Animals ; Female ; Mice ; Pregnancy ; Cell Differentiation ; Killer Cells, Natural ; Transcription Factors/metabolism ; Uterus/metabolism ; Receptors, Interleukin-21/metabolism ; STAT3 Transcription Factor/metabolism ; Signal Transduction
Chemical Substances	Transcription Factors ; Receptors, Interleukin-21 ; STAT3 Transcription Factor
Language	English
Publishing date	2023-11-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-42990-0
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Induction of local immunosuppression in allogeneic cell transplantation by cell-type-specific expression of PD-L1 and CTLA4Ig.

Zhu, Wenliang / Li, Mengqi / Zou, Jun / Zhang, Da / Fang, Minghui / Sun, Yun / Li, Can / Tang, Mingming / Wang, Yukai / Zhou, Qi / Zhao, Tongbiao / Li, Wei / Hu, Zheng / Hu, Baoyang

Stem cell reports

2023 Volume 18, Issue 12, Page(s) 2344–2355

Abstract: Immune rejection has long hindered allogeneic cell transplantation therapy. Current genetic modification approaches, including direct targeting of major histocompatibility complex or constitutive expression of immune inhibitory molecules, exhibit ... ...

Abstract	Immune rejection has long hindered allogeneic cell transplantation therapy. Current genetic modification approaches, including direct targeting of major histocompatibility complex or constitutive expression of immune inhibitory molecules, exhibit drawbacks such as severe adverse effects or elevated tumorigenesis risks. To overcome these limitations, we introduce an innovative approach to induce cell-type-specific immune tolerance in differentiated cells. By engineering human embryonic stem cells, we ensure the exclusive production of the immune inhibitory molecules PD-L1/CTLA4Ig in differentiated cells. Using this strategy, we generated hepatocyte-like cells expressing PD-L1 and CTLA4Ig, which effectively induced local immunotolerance. This approach was evaluated in a humanized mouse model that mimics the human immune system dynamics. We thus demonstrate a robust and selective induction of immunotolerance specific to hepatocytes, improving graft survival without observed tumorigenesis. This precise immune tolerance strategy holds great promise for advancing the development of stem cell-based therapeutics in regenerative medicine.
MeSH term(s)	Animals ; Humans ; Mice ; Abatacept ; B7-H1 Antigen/genetics ; Carcinogenesis ; Graft Survival ; Hematopoietic Stem Cell Transplantation ; Immune Tolerance ; Immunosuppression Therapy
Chemical Substances	Abatacept (7D0YB67S97) ; B7-H1 Antigen
Language	English
Publishing date	2023-11-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	2720528-9
ISSN	2213-6711 ; 2213-6711
ISSN (online)	2213-6711
ISSN	2213-6711
DOI	10.1016/j.stemcr.2023.10.016
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