Cell RegenerationPub Date : 2022-10-03DOI: 10.1186/s13619-022-00138-3
Ning Huang, Zu-Hang Sheng
{"title":"Microfluidic devices as model platforms of CNS injury-ischemia to study axonal regeneration by regulating mitochondrial transport and bioenergetic metabolism.","authors":"Ning Huang, Zu-Hang Sheng","doi":"10.1186/s13619-022-00138-3","DOIUrl":"https://doi.org/10.1186/s13619-022-00138-3","url":null,"abstract":"<p><p>Central nervous system (CNS) neurons typically fail to regenerate their axons after injury leading to neurological impairment. Axonal regeneration is a highly energy-demanding cellular program that requires local mitochondria to supply most energy within injured axons. Recent emerging lines of evidence have started to reveal that injury-triggered acute mitochondrial damage and local energy crisis contribute to the intrinsic energetic restriction that accounts for axon regeneration failure in the CNS. Characterizing and reprogramming bioenergetic signaling and mitochondrial maintenance after axon injury-ischemia is fundamental for developing therapeutic strategies that can restore local energy metabolism and thus facilitate axon regeneration. Therefore, establishing reliable and reproducible neuronal model platforms is critical for assessing axonal energetic metabolism and regeneration capacity after injury-ischemia. In this focused methodology article, we discuss recent advances in applying cutting-edge microfluidic chamber devices in combination with state-of-the-art live-neuron imaging tools to monitor axonal regeneration, mitochondrial transport, bioenergetic metabolism, and local protein synthesis in response to injury-ischemic stress in mature CNS neurons.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":" ","pages":"33"},"PeriodicalIF":0.0,"publicationDate":"2022-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9527262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40386465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell RegenerationPub Date : 2022-10-02DOI: 10.1186/s13619-022-00132-9
Daoming Chen, Zijian Xu, Jun Cui, Ting Chen
{"title":"A mouse model of vitiligo based on endogenous auto-reactive CD8 + T cell targeting skin melanocyte.","authors":"Daoming Chen, Zijian Xu, Jun Cui, Ting Chen","doi":"10.1186/s13619-022-00132-9","DOIUrl":"https://doi.org/10.1186/s13619-022-00132-9","url":null,"abstract":"<p><p>Vitiligo is the most common human skin depigmenting disorder. It is mediated by endogenous autoreactive CD8 + T cells that destruct skin melanocytes. This disease has an estimated prevalence of 1% of the global population and currently has no cure. Animal models are indispensable tools for understanding vitiligo pathogenesis and for developing new therapies. Here, we describe a vitiligo mouse model which recapitulates key clinical features of vitiligo, including epidermis depigmentation, CD8 + T cell infiltration in skin, and melanocyte loss. To activate endogenous autoreactive cytotoxic CD8 + T cells targeting melanocytes, this model relies on transient inoculation of B16F10 melanoma cells and depletion of CD4 + regulatory T cells. At cellular level, epidermal CD8 + T cell infiltration and melanocyte loss start as early as Day 19 after treatment. Visually apparent epidermis depigmentation occurs 2 months later. This protocol can efficiently induce vitiligo in any C57BL/6 background mouse strain, using only commercially available reagents. This enables researchers to carry out in-depth in vivo vitiligo studies utilizing mouse genetics tools, and provides a powerful platform for drug discovery.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":" ","pages":"31"},"PeriodicalIF":0.0,"publicationDate":"2022-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9526765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40388653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell RegenerationPub Date : 2022-10-01DOI: 10.1186/s13619-022-00130-x
Kaiming Xu, Guangshuo Ou
{"title":"Cilia regeneration requires an RNA splicing factor from the ciliary base.","authors":"Kaiming Xu, Guangshuo Ou","doi":"10.1186/s13619-022-00130-x","DOIUrl":"https://doi.org/10.1186/s13619-022-00130-x","url":null,"abstract":"<p><p>Cilia are microtubule-based organelles projected from most eukaryotic cell surfaces performing cell motility and signaling. Several previously recognized non-ciliary proteins play crucial roles in cilium formation and function. Here, we provide additional evidence that the Caenorhabditis elegans RNA splicing factor PRP-8/PRPF8 regulates ciliogenesis and regeneration from the ciliary base. Live imaging of GFP knock-in animals reveals that the endogenous PRP-8 localizes in the nuclei and the ciliary base. A weak loss-of-function allele of prp-8 affects ciliary structure but with little impact on RNA splicing. Conditional degradation of PRP-8 within ciliated sensory neurons showed its direct and specific roles in cilium formation. Notably, the penetrance of ciliary defects correlates with the reduction of PRP-8 at the ciliary base but not nuclei, and sensory neurons regenerated cilia accompanying PRP-8 recovery from the ciliary base rather than the nuclei. We suggest that PRP-8 at the ciliary base contributes to cilium formation and regeneration.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":" ","pages":"29"},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9525525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40386367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell RegenerationPub Date : 2022-09-19DOI: 10.1186/s13619-022-00131-w
Shixin Gong, Gongcheng Hu, Rong Guo, Jie Zhang, Yiqi Yang, Binrui Ji, Gang Li, Hongjie Yao
{"title":"CTCF acetylation at lysine 20 is required for the early cardiac mesoderm differentiation of embryonic stem cells.","authors":"Shixin Gong, Gongcheng Hu, Rong Guo, Jie Zhang, Yiqi Yang, Binrui Ji, Gang Li, Hongjie Yao","doi":"10.1186/s13619-022-00131-w","DOIUrl":"https://doi.org/10.1186/s13619-022-00131-w","url":null,"abstract":"<p><p>The CCCTC-binding factor (CTCF) protein and its modified forms regulate gene expression and genome organization. However, information on CTCF acetylation and its biological function is still lacking. Here, we show that CTCF can be acetylated at lysine 20 (CTCF-K20) by CREB-binding protein (CBP) and deacetylated by histone deacetylase 6 (HDAC6). CTCF-K20 is required for the CTCF interaction with CBP. A CTCF point mutation at lysine 20 had no effect on self-renewal but blocked the mesoderm differentiation of mouse embryonic stem cells (mESCs). The CTCF-K20 mutation reduced CTCF binding to the promoters and enhancers of genes associated with early cardiac mesoderm differentiation, resulting in diminished chromatin accessibility and decreased enhancer-promoter interactions, impairing gene expression. In summary, this study reveals the important roles of CTCF-K20 in regulating CTCF genomic functions and mESC differentiation into mesoderm.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":" ","pages":"34"},"PeriodicalIF":0.0,"publicationDate":"2022-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9482892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40363538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell RegenerationPub Date : 2022-09-03DOI: 10.1186/s13619-022-00135-6
Peng Jiang, Mahabub Maraj Alam
{"title":"Rise of the human-mouse chimeric brain models.","authors":"Peng Jiang, Mahabub Maraj Alam","doi":"10.1186/s13619-022-00135-6","DOIUrl":"https://doi.org/10.1186/s13619-022-00135-6","url":null,"abstract":"<p><p>Human-mouse chimeras offer advantages for studying the pathophysiology of human cells in vivo. Chimeric mouse brains have been created by engrafting human fetal tissue- or pluripotent stem cell-derived progenitor cells into the neonatal mouse brain. This provides new opportunities to understand human brain development and neurological disorders.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":" ","pages":"32"},"PeriodicalIF":0.0,"publicationDate":"2022-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9440171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40344963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell RegenerationPub Date : 2022-09-02DOI: 10.1186/s13619-022-00128-5
Chunmei Yue, Su Feng, Yingying Chen, Naihe Jing
{"title":"The therapeutic prospects and challenges of human neural stem cells for the treatment of Alzheimer's Disease.","authors":"Chunmei Yue, Su Feng, Yingying Chen, Naihe Jing","doi":"10.1186/s13619-022-00128-5","DOIUrl":"https://doi.org/10.1186/s13619-022-00128-5","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder associated with aging. Due to its insidious onset, protracted progression, and unclear pathogenesis, it is considered one of the most obscure and intractable brain disorders, and currently, there are no effective therapies for it. Convincing evidence indicates that the irreversible decline of cognitive abilities in patients coincides with the deterioration and degeneration of neurons and synapses in the AD brain. Human neural stem cells (NSCs) hold the potential to functionally replace lost neurons, reinforce impaired synaptic networks, and repair the damaged AD brain. They have therefore received extensive attention as a possible source of donor cells for cellular replacement therapies for AD. Here, we review the progress in NSC-based transplantation studies in animal models of AD and assess the therapeutic advantages and challenges of human NSCs as donor cells. We then formulate a promising transplantation approach for the treatment of human AD, which would help to explore the disease-modifying cellular therapeutic strategy for the treatment of human AD.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":" ","pages":"28"},"PeriodicalIF":0.0,"publicationDate":"2022-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9437172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40340536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Intestinal cellular heterogeneity and disease development revealed by single-cell technology.","authors":"Yalong Wang, Wanlu Song, Shicheng Yu, Yuan Liu, Ye-Guang Chen","doi":"10.1186/s13619-022-00127-6","DOIUrl":"https://doi.org/10.1186/s13619-022-00127-6","url":null,"abstract":"<p><p>The intestinal epithelium is responsible for food digestion and nutrient absorption and plays a critical role in hormone secretion, microorganism defense, and immune response. These functions depend on the integral single-layered intestinal epithelium, which shows diversified cell constitution and rapid self-renewal and presents powerful regeneration plasticity after injury. Derailment of homeostasis of the intestine epithelium leads to the development of diseases, most commonly including enteritis and colorectal cancer. Therefore, it is important to understand the cellular characterization of the intestinal epithelium at the molecular level and the mechanisms underlying its homeostatic maintenance. Single-cell technologies allow us to gain molecular insights at the single-cell level. In this review, we summarize the single-cell RNA sequencing applications to understand intestinal cell characteristics, spatiotemporal evolution, and intestinal disease development.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":" ","pages":"26"},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9433512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40333615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell RegenerationPub Date : 2022-08-03DOI: 10.1186/s13619-022-00126-7
Deepti Abbey
{"title":"Chemical journey of somatic cells to pluripotency.","authors":"Deepti Abbey","doi":"10.1186/s13619-022-00126-7","DOIUrl":"https://doi.org/10.1186/s13619-022-00126-7","url":null,"abstract":"<p><p>Reprogramming somatic cells to pluripotent stem cells has revolutionized the biomedical field by providing enormous hopes and opportunities for the regeneration of tissues and organs for transplantation. Using a small molecule cocktail of epigenetic modifiers and cell signalling inhibitors, a chemical-based easy and controllable technique for converting human somatic cells into chemically induced pluripotent stem cells was recently reported (Guan, Nature 605:325-31, 2022). This novel approach offers well-defined, safe, simple, easy, and clinical-grade manufacturing strategies for modifying the fate of human cells required for regenerative therapeutics.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":" ","pages":"27"},"PeriodicalIF":0.0,"publicationDate":"2022-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9346013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40595552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell RegenerationPub Date : 2022-08-02DOI: 10.1186/s13619-022-00124-9
Lu Li, Pishun Li, Jiale Chen, Li Li, Yunfan Shen, Yangzixuan Zhu, Jiayi Liu, Lu Lv, Song Mao, Fang Chen, Guang Hu, Kai Yuan
{"title":"Rif1 interacts with non-canonical polycomb repressive complex PRC1.6 to regulate mouse embryonic stem cells fate potential.","authors":"Lu Li, Pishun Li, Jiale Chen, Li Li, Yunfan Shen, Yangzixuan Zhu, Jiayi Liu, Lu Lv, Song Mao, Fang Chen, Guang Hu, Kai Yuan","doi":"10.1186/s13619-022-00124-9","DOIUrl":"https://doi.org/10.1186/s13619-022-00124-9","url":null,"abstract":"<p><p>Mouse embryonic stem cells (mESCs) cycle in and out of a transient 2-cell (2C)-like totipotent state, driven by a complex genetic circuit involves both the coding and repetitive sections of the genome. While a vast array of regulators, including the multi-functional protein Rif1, has been reported to influence the switch of fate potential, how they act in concert to achieve this cellular plasticity remains elusive. Here, by modularizing the known totipotency regulatory factors, we identify an unprecedented functional connection between Rif1 and the non-canonical polycomb repressive complex PRC1.6. Downregulation of the expression of either Rif1 or PRC1.6 subunits imposes similar impacts on the transcriptome of mESCs. The LacO-LacI induced ectopic colocalization assay detects a specific interaction between Rif1 and Pcgf6, bolstering the intactness of the PRC1.6 complex. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) analysis further reveals that Rif1 is required for the accurate targeting of Pcgf6 to a group of genomic loci encompassing many genes involved in the regulation of the 2C-like state. Depletion of Rif1 or Pcgf6 not only activates 2C genes such as Zscan4 and Zfp352, but also derepresses a group of the endogenous retroviral element MERVL, a key marker for totipotency. Collectively, our findings discover that Rif1 can serve as a novel auxiliary component in the PRC1.6 complex to restrain the genetic circuit underlying totipotent fate potential, shedding new mechanistic insights into its function in regulating the cellular plasticity of embryonic stem cells.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":" ","pages":"25"},"PeriodicalIF":0.0,"publicationDate":"2022-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40662733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}