{"title":"Identification of feature genes in intestinal epithelial cell types.","authors":"Ruoyu Lou, Wanlu Song, Shicheng Yu, Xiaodan Wang, Yuan Liu, Ye-Guang Chen, Yalong Wang","doi":"10.1186/s13619-024-00208-8","DOIUrl":"10.1186/s13619-024-00208-8","url":null,"abstract":"<p><p>The intestine, is responsible for food digestion, nutrient absorption, endocrine secretion, food residue excretion, and immune defense. These function performances are based on the intricate composition of intestinal epithelial cells, encompassing differentiated mature cells, rapidly proliferative cells, and intestinal stem cells. Although the characteristics of these cell types are well-documented, in-depth exploration of their representative markers and transcription factors is critical for comprehensive cell fate trajectory analysis. Here, we unveiled the feature genes in different cell types of the human and mouse gut through single-cell RNA sequencing analysis. Further, the locations of some specific transcription factors and membrane proteins were determined by immunofluorescence staining, and their role in regulating the proliferation and differentiation of intestinal epithelial cells were explored by CRISPR/Cas9 knockout. Therefore, this study not only reports new markers for various intestinal epithelial cell types but also elucidates the involvement of relevant genes in the determination of epithelial cell fate and maintenance of stem cell homeostasis, which facilitates the tracing and functional elucidation of intestinal epithelial cells.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"13 1","pages":"24"},"PeriodicalIF":4.0,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11564585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615455","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":"Application and new findings of scRNA-seq and ST-seq in prostate cancer.","authors":"Zhuang Li, Zhengnan Li, Yuanyuan Luo, Weiming Chen, Yinyi Fang, Yuliang Xiong, Qinyi Zhang, Dongbo Yuan, Bo Yan, Jianguo Zhu","doi":"10.1186/s13619-024-00206-w","DOIUrl":"10.1186/s13619-024-00206-w","url":null,"abstract":"<p><p>Prostate cancer is a malignant tumor of the male urological system with the highest incidence rate in the world, which seriously threatens the life and health of middle-aged and elderly men. The progression of prostate cancer involves the interaction between tumor cells and tumor microenvironment. Understanding the mechanisms of prostate cancer pathogenesis and disease progression is important to guide diagnosis and therapy. The emergence of single-cell RNA sequencing (scRNA-seq) and spatial transcriptome sequencing (ST-seq) technologies has brought breakthroughs in the study of prostate cancer. It makes up for the defects of traditional techniques such as fluorescence-activated cell sorting that are difficult to elucidate cell-specific gene expression. This review summarized the heterogeneity and functional changes of prostate cancer and tumor microenvironment revealed by scRNA-seq and ST-seq, aims to provide a reference for the optimal diagnosis and treatment of prostate cancer.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"13 1","pages":"23"},"PeriodicalIF":4.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11522250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543949","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 : 2024-10-11DOI: 10.1186/s13619-024-00205-x
Qianfeng Xiang, Lei Li, Wei Ji, Debby Gawlitta, X Frank Walboomers, Jeroen J J P van den Beucken
{"title":"Beyond resorption: osteoclasts as drivers of bone formation.","authors":"Qianfeng Xiang, Lei Li, Wei Ji, Debby Gawlitta, X Frank Walboomers, Jeroen J J P van den Beucken","doi":"10.1186/s13619-024-00205-x","DOIUrl":"10.1186/s13619-024-00205-x","url":null,"abstract":"<p><p>Emerging evidence illustrates that osteoclasts (OCs) play diverse roles beyond bone resorption, contributing significantly to bone formation and regeneration. Despite this, OCs remain mysterious cells, with aspects of their lifespan-from origin, fusion, alterations in cellular characteristics, to functions-remaining incompletely understood. Recent studies have identified that embryonic osteoclastogenesis is primarily driven by osteoclast precursors (OCPs) derived from erythromyeloid progenitors (EMPs). These precursor cells subsequently fuse into OCs essential for normal bone development and repair. Postnatally, hematopoietic stem cells (HSCs) become the primary source of OCs, gradually replacing EMP-derived OCs and assuming functional roles in adulthood. The absence of OCs during bone development results in bone structure malformation, including abnormal bone marrow cavity formation and shorter long bones. Additionally, OCs are reported to have intimate interactions with blood vessels, influencing bone formation and repair through angiogenesis regulation. Upon biomaterial implantation, activation of the innate immune system ensues immediately. OCs, originating from macrophages, closely interact with the immune system. Furthermore, evidence from material-induced bone formation events suggests that OCs are pivotal in these de novo bone formation processes. Nevertheless, achieving a pure OC culture remains challenging, and interpreting OC functions in vivo faces difficulties due to the presence of other multinucleated cells around bone-forming biomaterials. We here describe the fusion characteristics of OCPs and summarize reliable markers and morphological changes in OCs during their fusion process, providing guidance for researchers in identifying OCs both in vitro and in vivo. This review focuses on OC formation, characterization, and the roles of OCs beyond resorption in various bone pathophysiological processes. Finally, therapeutic strategies targeting OCs are discussed.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"13 1","pages":"22"},"PeriodicalIF":4.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11469995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399544","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 : 2024-10-10DOI: 10.1186/s13619-024-00204-y
Ran Tao, Chunmei Yue, Zhijie Guo, Wenke Guo, Yao Yao, Xianfa Yang, Zhen Shao, Chao Gao, Jianqing Ding, Lu Shen, Shengdi Chen, Naihe Jing
{"title":"Subtype-specific neurons from patient iPSCs display distinct neuropathological features of Alzheimer's disease.","authors":"Ran Tao, Chunmei Yue, Zhijie Guo, Wenke Guo, Yao Yao, Xianfa Yang, Zhen Shao, Chao Gao, Jianqing Ding, Lu Shen, Shengdi Chen, Naihe Jing","doi":"10.1186/s13619-024-00204-y","DOIUrl":"https://doi.org/10.1186/s13619-024-00204-y","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by massive neuronal loss in the brain. Both cortical glutamatergic neurons and basal forebrain cholinergic neurons (BFCNs) in the AD brain are selectively vulnerable. The degeneration and dysfunction of these two subtypes of neurons are closely associated with the cognitive decline of AD patients. The determination of cellular and molecular mechanisms involved in AD pathogenesis, especially in the early stage, will largely facilitate the understanding of this disease and the development of proper intervention strategies. However, due to the inaccessibility of living neurons in the brains of patients, it remains unclear how cortical glutamatergic neurons and BFCNs respond to pathological stress in the early stage of AD. In this study, we established in vitro differentiation systems that can efficiently differentiate patient-derived iPSCs into BFCNs. We found that AD-BFCNs secreted less Aβ peptide than cortical glutamatergic neurons did, even though the Aβ42/Aβ40 ratio was comparable to that of cortical glutamatergic neurons. To further mimic the neurotoxic niche in AD brain, we treated iPSC-derived neurons with Aβ42 oligomer (AβO). BFCNs are less sensitive to AβO induced tau phosphorylation and expression than cortical glutamatergic neurons. However, AβO could trigger apoptosis in both AD-cortical glutamatergic neurons and AD-BFCNs. In addition, AD iPSC-derived BFCNs and cortical glutamatergic neurons exhibited distinct electrophysiological firing patterns and elicited different responses to AβO treatment. These observations revealed that subtype-specific neurons display distinct neuropathological changes during the progression of AD, which might help to understand AD pathogenesis at the cellular level.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"13 1","pages":"21"},"PeriodicalIF":4.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459185","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 : 2024-10-02DOI: 10.1186/s13619-024-00201-1
Yuan Yu, Kaixuan Lin, Haoyu Wu, Mingli Hu, Xuejie Yang, Jie Wang, Johannes Grillari, Jiekai Chen
{"title":"Targeting senescent cells in aging and COVID-19: from cellular mechanisms to therapeutic opportunities.","authors":"Yuan Yu, Kaixuan Lin, Haoyu Wu, Mingli Hu, Xuejie Yang, Jie Wang, Johannes Grillari, Jiekai Chen","doi":"10.1186/s13619-024-00201-1","DOIUrl":"10.1186/s13619-024-00201-1","url":null,"abstract":"<p><p>The COVID-19 pandemic has caused a global health crisis and significant social economic burden. While most individuals experience mild or non-specific symptoms, elderly individuals are at a higher risk of developing severe symptoms and life-threatening complications. Exploring the key factors associated with clinical severity highlights that key characteristics of aging, such as cellular senescence, immune dysregulation, metabolic alterations, and impaired regenerative potential, contribute to disruption of tissue homeostasis of the lung and worse clinical outcome. Senolytic and senomorphic drugs, which are anti-aging treatments designed to eliminate senescent cells or decrease the associated phenotypes, have shown promise in alleviating age-related dysfunctions and offer a novel approach to treating diseases that share certain aspects of underlying mechanisms with aging, including COVID-19. This review summarizes the current understanding of aging in COVID-19 progression, and highlights recent findings on anti-aging drugs that could be repurposed for COVID-19 treatment to complement existing therapies.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"13 1","pages":"20"},"PeriodicalIF":4.0,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364575","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 : 2024-09-30DOI: 10.1186/s13619-024-00203-z
Xinyang Li, Gaoxiang Zhu, Bing Zhao
{"title":"Chromatin remodeling in tissue stem cell fate determination.","authors":"Xinyang Li, Gaoxiang Zhu, Bing Zhao","doi":"10.1186/s13619-024-00203-z","DOIUrl":"10.1186/s13619-024-00203-z","url":null,"abstract":"<p><p>Tissue stem cells (TSCs), which reside in specialized tissues, constitute the major cell sources for tissue homeostasis and regeneration, and the contribution of transcriptional or epigenetic regulation of distinct biological processes in TSCs has been discussed in the past few decades. Meanwhile, ATP-dependent chromatin remodelers use the energy from ATP hydrolysis to remodel nucleosomes, thereby affecting chromatin dynamics and the regulation of gene expression programs in each cell type. However, the role of chromatin remodelers in tissue stem cell fate determination is less well understood. In this review, we systematically discuss recent advances in epigenetic control by chromatin remodelers of hematopoietic stem cells, intestinal epithelial stem cells, neural stem cells, and skin stem cells in their fate determination and highlight the importance of their essential role in tissue homeostasis, development, and regeneration. Moreover, the exploration of the molecular and cellular mechanisms of TSCs is crucial for advancing our understanding of tissue maintenance and for the discovery of novel therapeutic targets.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"13 1","pages":"18"},"PeriodicalIF":4.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11442411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342504","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 : 2024-09-30DOI: 10.1186/s13619-024-00202-0
Xueli Hu, Jianjian Sun, Meng Wan, Bianhong Zhang, Linhui Wang, Tao P Zhong
{"title":"Expression levels and stoichiometry of Hnf1β, Emx2, Pax8 and Hnf4 influence direct reprogramming of induced renal tubular epithelial cells.","authors":"Xueli Hu, Jianjian Sun, Meng Wan, Bianhong Zhang, Linhui Wang, Tao P Zhong","doi":"10.1186/s13619-024-00202-0","DOIUrl":"10.1186/s13619-024-00202-0","url":null,"abstract":"<p><p>Generation of induced renal epithelial cells (iRECs) from fibroblasts offers great opportunities for renal disease modeling and kidney regeneration. However, the low reprogramming efficiency of the current approach to generate iRECs has hindered potential therapeutic application and regenerative approach. This could be in part attributed to heterogeneous and unbalanced expression of reprogramming factors (RFs) Hnf1β (H1), Emx2 (E), Pax8 (P), and Hnf4α (H4) in transduced fibroblasts. Here, we establish an advanced retroviral vector system that expresses H1, E, P, and H4 in high levels and distinct ratios from bicistronic transcripts separated by P2A. Mouse embryonic fibroblasts (MEFs) harboring Cdh16-Cre; mT/mG allele are utilized to conduct iREC reprogramming via directly monitoring single cell fate conversion. Three sets of bicistronic RF combinations including H1E/H4P, H1H4/EP, and H1P/H4E have been generated to induce iREC reprogramming. Each of the RF combinations gives rise to distinct H1, E, P, and H4 expression levels and different reprogramming efficiencies. The desired H1E/H4P combination that results in high expression levels of RFs with balanced stoichiometry. substantially enhances the efficiency and quality of iRECs compared with transduction of separate H1, E, P, and H4 lentiviruses. We find that H1E/H4P-induced iRECs exhibit the superior features of renal tubular epithelial cells, as evidenced by expressing renal tubular-specific genes, possessing endocytotic arrogation activity and assembling into tubules along decellularized kidney scaffolds. This study establishes H1E/H4P cassette as a valuable platform for future iREC studies and regenerative medicine.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"13 1","pages":"19"},"PeriodicalIF":4.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11442758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342505","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 : 2024-09-13DOI: 10.1186/s13619-024-00200-2
Yuling Peng, Jieying Zhu, Qi Zhang, Ran Zhang, Zhenhua Wang, Zesen Ye, Ning Ma, Dajiang Qin, Duanqing Pei, Dongwei Li
{"title":"Endogenous retroviral ERVH48-1 promotes human urine cell reprogramming.","authors":"Yuling Peng, Jieying Zhu, Qi Zhang, Ran Zhang, Zhenhua Wang, Zesen Ye, Ning Ma, Dajiang Qin, Duanqing Pei, Dongwei Li","doi":"10.1186/s13619-024-00200-2","DOIUrl":"https://doi.org/10.1186/s13619-024-00200-2","url":null,"abstract":"<p><p>Endogenous retroviruses (ERVs), once thought to be mere remnants of ancient viral integrations in the mammalian genome, are now recognized for their critical roles in various physiological processes, including embryonic development, innate immunity, and tumorigenesis. Their impact on host organisms is significant driver of evolutionary changes, offering insight into evolutionary mechanisms. In our study, we explored the functionality of ERVs by examining single-cell transcriptomic profiles from human embryonic stem cells and urine cells. This led to the discovery of a unique ERVH48-1 expression pattern between these cell types. Additionally, somatic cell reprogramming efficacy was enhanced when ERVH48-1 was overexpressed in a urine cell-reprogramming system. Induced pluripotent stem cells (iPSCs) generated with ERVH48-1 overexpression recapitulated the traits of those produced by traditional reprogramming approaches, and the resulting iPSCs demonstrated the capability to differentiate into all three germ layers in vitro. Our research elucidated the role of ERVs in somatic cell reprogramming.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"13 1","pages":"17"},"PeriodicalIF":4.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11399365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280978","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":"Standard: human intestine-on-a-chip.","authors":"Haitao Liu, Yaqing Wang, Xu Zhang, Min Zhang, Peng Wang, Jing Shang, Zhongqiang Li, Likun Gong, Jiabin Guo, Wei Sun, Jingbo Pi, Xianliang Li, Wei Ding, Dianbing Wang, Zhongyu Li, Jingzhong Zhang, Lan Wang, Xingchao Geng, Ruifu Yang, Pingkun Zhou, Wanjin Tang, Xian'en Zhang, Chunying Chen, Shengli Yang, Jianhua Qin","doi":"10.1186/s13619-024-00198-7","DOIUrl":"10.1186/s13619-024-00198-7","url":null,"abstract":"<p><p>Organs-on-chips are microphysiological systems that allow to replicate the key functions of human organs and accelerate the innovation in life sciences including disease modeling, drug development, and precision medicine. However, due to the lack of standards in their definition, structural design, cell source, model construction, and functional validation, a wide range of translational application of organs-on-chips remains a challenging. \"Organs-on-chips: Intestine\" is the first group standard on human intestine-on-a-chip in China, jointly agreed and released by the experts from the Chinese Society of Biotechnology on 29th April 2024. This standard specifies the scope, terminology, definitions, technical requirements, detection methods, and quality control in building the human intestinal model on a chip. The publication of this group standard will guide the institutional establishment, acceptance and execution of proper practical protocols and accelerate the international standardization of intestine-on-a-chip for translational applications.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"13 1","pages":"16"},"PeriodicalIF":4.0,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11300753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888594","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}