{"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}
Cell RegenerationPub Date : 2022-08-01DOI: 10.1186/s13619-022-00125-8
Wenwen Jin, Wei Jiang
{"title":"Stepwise differentiation of functional pancreatic β cells from human pluripotent stem cells.","authors":"Wenwen Jin, Wei Jiang","doi":"10.1186/s13619-022-00125-8","DOIUrl":"https://doi.org/10.1186/s13619-022-00125-8","url":null,"abstract":"<p><p>Pancreatic β cells differentiated from stem cells provide promise for cell replacement therapy of diabetes. Human pluripotent stem cells could be differentiated into definitive endoderm, followed by pancreatic progenitors, and then subjected to endocrinal differentiation and maturation in a stepwise fashion. Many achievements have been made in making pancreatic β cells from human pluripotent stem cells in last two decades, and a couple of phase I/II clinical trials have just been initiated. Here, we overview the major progresses in differentiating pancreatic β cells from human pluripotent stem cells with the focus on recent technical advances in each differentiation stage, and briefly discuss the current limitations as well.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":" ","pages":"24"},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9339430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40669883","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 : 2022-07-02DOI: 10.1186/s13619-022-00123-w
Xin-Xin Han, Shengkai Jin, Li-Ming Yu, Min Wang, Xin-Yu Hu, Dai-Yu Hu, Jie Ren, Meng-Han Zhang, Wei Huang, Jia-Jia Deng, Qing-Qing Chen, Zhengliang Gao, Hua He, Chunhui Cai
{"title":"Interferon-beta inhibits human glioma stem cell growth by modulating immune response and cell cycle related signaling pathways.","authors":"Xin-Xin Han, Shengkai Jin, Li-Ming Yu, Min Wang, Xin-Yu Hu, Dai-Yu Hu, Jie Ren, Meng-Han Zhang, Wei Huang, Jia-Jia Deng, Qing-Qing Chen, Zhengliang Gao, Hua He, Chunhui Cai","doi":"10.1186/s13619-022-00123-w","DOIUrl":"https://doi.org/10.1186/s13619-022-00123-w","url":null,"abstract":"<p><p>Malignant Glioma is characterized by strong self-renewal potential and immature differentiation potential. The main reason is that malignant glioma holds key cluster cells, glioma stem cells (GSCs). GSCs contribute to tumorigenesis, tumor progression, recurrence, and treatment resistance. Interferon-beta (IFN-β) is well known for its anti-proliferative efficacy in diverse cancers. IFN-β also displayed potent antitumor effects in malignant glioma. IFN-β affect both GSCs and Neural stem cells (NSCs) in the treatment of gliomas. However, the functional comparison, similar or different effects of IFN-β on GSCs and NSCs are rarely reported. Here, we studied the similarities and differences of the responses to IFN-β between human GSCs and normal NSCs. We found that IFN-β preferentially inhibited GSCs over NSCs. The cell body and nucleus size of GSCs increased after IFN-β treatment, and the genomic analysis revealed the enrichment of the upregulated immune response, cell adhesion genes and down regulated cell cycle, ribosome pathways. Several typical cyclin genes, including cyclin A2 (CCNA2), cyclin B1 (CCNB1), cyclin B2 (CCNB2), and cyclin D1 (CCND1), were significantly downregulated in GSCs after IFN-β stimulation. We also found that continuous IFN-β stimulation after passage further enhanced the inhibitory effect. Our study revealed how genetic diversity resulted in differential effects in response to IFN-β treatment. These results may contribute to improve the applications of IFN-β in anti-cancer immunotherapy. In addition, these results may also help to design more effective pharmacological strategies to target cancer stem cells while protecting normal neural stem cells.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":" ","pages":"23"},"PeriodicalIF":0.0,"publicationDate":"2022-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9249963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40564668","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 : 2022-07-01DOI: 10.1186/s13619-022-00122-x
Zhicao Yue, Fang Yang, Jianglin Zhang, Ji Li, Cheng-Ming Chuong
{"title":"Regulation and dysregulation of hair regeneration: aiming for clinical application.","authors":"Zhicao Yue, Fang Yang, Jianglin Zhang, Ji Li, Cheng-Ming Chuong","doi":"10.1186/s13619-022-00122-x","DOIUrl":"https://doi.org/10.1186/s13619-022-00122-x","url":null,"abstract":"<p><p>Hair growth and regeneration represents a remarkable example of stem cell function. Recent progress emphasizes the micro- and macro- environment that controls the regeneration process. There is a shift from a stem cell-centered view toward the various layers of regulatory mechanisms that control hair regeneration, which include local growth factors, immune and neuroendocrine signals, and dietary and environmental factors. This is better suited for clinical application in multiple forms of hair disorders: in male pattern hair loss, the stem cells are largely preserved, but androgen signaling diminishes hair growth; in alopecia areata, an immune attack is targeted toward the growing hair follicle without abrogating its regeneration capability. Genome-wide association studies further revealed the genetic bases of these disorders, although the precise pathological mechanisms of the identified loci remain largely unknown. By analyzing the dysregulation of hair regeneration under pathological conditions, we can better address the complex interactions among stem cells, the differentiated progeny, and mesenchymal components, and highlight the critical role of macroenvironment adjustment that is essential for hair growth and regeneration. The poly-genetic origin of these disorders makes the study of hair regeneration an interesting and challenging field.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":" ","pages":"22"},"PeriodicalIF":0.0,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9247129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40461320","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 : 2022-06-02DOI: 10.1186/s13619-022-00121-y
Xing Qin, Juanjuan Fei, Yu Duan, Asli F Ceylan, Fuyang Zhang, Jun Ren
{"title":"Beclin1 haploinsufficiency compromises mesenchymal stem cell-offered cardioprotection against myocardial infarction.","authors":"Xing Qin, Juanjuan Fei, Yu Duan, Asli F Ceylan, Fuyang Zhang, Jun Ren","doi":"10.1186/s13619-022-00121-y","DOIUrl":"10.1186/s13619-022-00121-y","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs)-based therapy has displayed some promises in ischemia heart diseases although its efficacy may be affected by changes in surrounding environments. This study evaluated the role of autophagy insufficiency using Beclin1 haploinsufficiency (BECN<sup>+/-</sup>) on intra-myocardial MSC transplantation-evoked effect against myocardial infarction. Donor MSCs from C57BL/6 mice were labelled with cell-tracker CM Dil and were delivered into LV free wall adjacent to infarct region in wild-type (WT) and BECN<sup>+/-</sup> recipient mice following ligation of left main coronary artery (MI-MSCs). Ten days following MI, myocardial function was assessed using echocardiography. Cardiomyocyte contractility and intracellular Ca<sup>2+</sup> were monitored using cardiomyocytes from the area-at-risk adjacent to infarct. CM-Dil labeled cells were tracked in MSCs recipient mice using fluorescence microscopy. Lectin, Masson trichrome staining and Western blot analysis were employed to determine cardiomyocyte area, scar fibrosis, apoptosis and inflammation. MI insult triggered scar fibrosis, LV chamber dilation, decreased fractional shortening, ejection fraction, cardiomyocyte shortening, maximal velocity of shortening and relengthening as well as prolonged relengthening, which were abrogated or attenuated by MSCs therapy in WT but not BECN<sup>+/-</sup> mice. MI decreased intracellular Ca<sup>2+</sup> rise and decay in response to electrical stimuli without affecting resting intracellular Ca<sup>2+</sup>, which were reconciled by MSCs in WT but not BECN<sup>+/-</sup> mice. MSCs further attenuated MI-induced mitochondrial ultrastructural injury, apoptosis, inflammation and autophagy defects in peri-infarct area in WT but not BECN<sup>+/-</sup> mice. Collectively, our results suggested that autophagy insufficiency dampened in MSCs-elicited cardioprotection associated with dampened apoptosis and inflammation.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"11 1","pages":"21"},"PeriodicalIF":4.0,"publicationDate":"2022-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9160171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65859751","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 : 2022-05-05DOI: 10.1186/s13619-022-00118-7
Haonan Li, Xiaodan Wang, Yalong Wang, Mengxian Zhang, F. Hong, Hong Wang, Along Cui, Jianguo Zhao, W. Ji, Ye-Guang Chen
{"title":"Cross-species single-cell transcriptomic analysis reveals divergence of cell composition and functions in mammalian ileum epithelium","authors":"Haonan Li, Xiaodan Wang, Yalong Wang, Mengxian Zhang, F. Hong, Hong Wang, Along Cui, Jianguo Zhao, W. Ji, Ye-Guang Chen","doi":"10.1186/s13619-022-00118-7","DOIUrl":"https://doi.org/10.1186/s13619-022-00118-7","url":null,"abstract":"","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43438279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}