{"title":"Mechanical stretching boosts expansion and regeneration of intestinal organoids through fueling stem cell self-renewal.","authors":"Fanlu Meng, Congcong Shen, Li Yang, Chao Ni, Jianyong Huang, Kaijun Lin, Zanxia Cao, Shicai Xu, Wanling Cui, Xiaoxin Wang, Bailing Zhou, Chunyang Xiong, Jihua Wang, Bing Zhao","doi":"10.1186/s13619-022-00137-4","DOIUrl":"https://doi.org/10.1186/s13619-022-00137-4","url":null,"abstract":"<p><p>Intestinal organoids, derived from intestinal stem cell self-organization, recapitulate the tissue structures and behaviors of the intestinal epithelium, which hold great potential for the study of developmental biology, disease modeling, and regenerative medicine. The intestinal epithelium is exposed to dynamic mechanical forces which exert profound effects on gut development. However, the conventional intestinal organoid culture system neglects the key role of mechanical microenvironments but relies solely on biological factors. Here, we show that adding cyclic stretch to intestinal organoid cultures remarkably up-regulates the signature gene expression and proliferation of intestinal stem cells. Furthermore, mechanical stretching stimulates the expansion of SOX9<sup>+</sup> progenitors by activating the Wnt/β-Catenin signaling. These data demonstrate that the incorporation of mechanical stretch boosts the stemness of intestinal stem cells, thus benefiting organoid growth. Our findings have provided a way to optimize an organoid generation system through understanding cross-talk between biological and mechanical factors, paving the way for the application of mechanical forces in organoid-based models.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":" ","pages":"39"},"PeriodicalIF":0.0,"publicationDate":"2022-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9626719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40659610","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":"Glioma stem cells and neural stem cells respond differently to BMP4 signaling.","authors":"Xin-Xin Han, Chunhui Cai, Li-Ming Yu, Min Wang, Wenhan Yang, Dai-Yu Hu, Jie Ren, Lu-Ying Zhu, Jia-Jia Deng, Qing-Qing Chen, Hua He, Zhengliang Gao","doi":"10.1186/s13619-022-00136-5","DOIUrl":"https://doi.org/10.1186/s13619-022-00136-5","url":null,"abstract":"<p><p>Malignant glioma is a highly heterogeneous and invasive primary brain tumor characterized by high recurrence rates, resistance to combined therapy, and dismal prognosis. Glioma stem cells (GSCs) are likely responsible for tumor progression, resistance to therapy, recurrence, and poor prognosis owing to their high self-renewal and tumorigenic potential. As a family member of BMP signaling, bone morphogenetic protein4 (BMP4) has been reported to induce the differentiation of GSCs and neural stem cells (NSCs). However, the molecular mechanisms underlying the BMP4-mediated effects in these two cell types are unclear. In this study, we treated hGSCs and hNSCs with BMP4 and compared the phenotypic and transcriptional changes between these two cell types. Phenotypically, we found that the growth of hGSCs was greatly inhibited by BMP4, but the same treatment only increased the cell size of hNSCs. While the RNA sequencing results showed that BMP4 treatment evoked significantly transcriptional changes in both hGSCs and hNSCs, the profiles of differentially expressed genes were distinct between the two groups. A gene set that specifically targeted the proliferation and differentiation of hGSCs but not hNSCs was enriched and then validated in hGSC culture. Our results suggested that hGSCs and hNSCs responded differently to BMP4 stimulation. Understanding and investigating different responses between hGSCs and hNSCs will benefit finding partner factors working together with BMP4 to further suppress GSCs proliferation and stemness without disturbing NSCs.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":" ","pages":"36"},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9622962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40658938","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 : 2022-10-19DOI: 10.1186/s13619-022-00144-5
Binxu Yin, Xinyun Li, Gufa Lin, Heng Wang
{"title":"High-resolution single-cell analysis paves the cellular path for brain regeneration in salamanders.","authors":"Binxu Yin, Xinyun Li, Gufa Lin, Heng Wang","doi":"10.1186/s13619-022-00144-5","DOIUrl":"https://doi.org/10.1186/s13619-022-00144-5","url":null,"abstract":"<p><p>Salamanders are excellent models for studying vertebrate brain regeneration, with the promise of developing novel therapies for human brain lesions. Yet the molecular and cellular mechanism of salamander brain regeneration remains largely elusive. The insight into the evolution of complex brain structures that lead to advanced functions in the mammalian brain is also inadequate. With high-resolution single-cell RNA sequencing and spatial transcriptomics, three recent studies have reported the differentiation paths of cells in the salamander telencephalon in the journal Science, bringing both old and new cell types into the focus and shedding light on vertebrate brain evolution, development, and regeneration.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":" ","pages":"37"},"PeriodicalIF":0.0,"publicationDate":"2022-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9579219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40337146","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 : 2022-10-03DOI: 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}