International journal of stem cells最新文献

{"title":"RNF43 and ZNRF3 in Wnt Signaling - A Master Regulator at the Membrane.","authors":"Fiona Farnhammer, Gabriele Colozza, Jihoon Kim","doi":"10.15283/ijsc23070","DOIUrl":"10.15283/ijsc23070","url":null,"abstract":"<p><p>The Wnt <i>β</i>-catenin signaling pathway is a highly conserved mechanism that plays a critical role from embryonic development and adult stem cell homeostasis. However, dysregulation of the Wnt pathway has been implicated in various diseases, including cancer. Therefore, multiple layers of regulatory mechanisms tightly control the activation and suppression of the Wnt signal. The E3 ubiquitin ligases RNF43 and ZNRF3, which are known negative regulators of the Wnt pathway, are critical component of Wnt signaling regulation. These E3 ubiquitin ligases control Wnt signaling by targeting the Wnt receptor Frizzled to induce ubiquitination-mediated endo-lysosomal degradation, thus controlling the activation of the Wnt signaling pathway. We also discuss the regulatory mechanisms, interactors, and evolution of RNF43 and ZNRF3. This review article summarizes recent findings on RNF43 and ZNRF3 and their potential implications for the development of therapeutic strategies to target the Wnt signaling pathway in various diseases, including cancer.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"376-384"},"PeriodicalIF":2.3,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10686798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10109943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adipose Tissue-Derived Mesenchymal Stromal Cells from Ex-Morbidly Obese Individuals Instruct Macrophages towards a M2-Like Profile <i>In Vitro</i>.","authors":"Daiana V Lopes Alves, Cesar Claudio-da-Silva, Marcelo C A Souza, Rosa T Pinho, Wellington Seguins da Silva, Periela S Sousa-Vasconcelos, Radovan Borojevic, Carmen M Nogueira, Hélio Dos S Dutra, Christina M Takiya, Danielle C Bonfim, Maria Isabel D Rossi","doi":"10.15283/ijsc22172","DOIUrl":"10.15283/ijsc22172","url":null,"abstract":"<p><p>Obesity, which continues to increase worldwide, was shown to irreversibly impair the differentiation potential and angiogenic properties of adipose tissue mesenchymal stromal cells (ADSCs). Because these cells are intended for regenerative medicine, especially for the treatment of inflammatory conditions, and the effects of obesity on the immunomodulatory properties of ADSCs are not yet clear, here we investigated how ADSCs isolated from former obese subjects (Ex-Ob) would influence macrophage differentiation and polarization, since these cells are the main instructors of inflammatory responses. Analysis of the subcutaneous adipose tissue (SAT) of overweight (OW) and Ex-Ob subjects showed the maintenance of approximately twice as many macrophages in Ex-Ob SAT, contained within the CD68^＋/FXIII-A^- inflammatory pool. Despite it, <i>in vitro</i>, coculture experiments revealed that Ex-Ob ADSCs instructed monocyte differentiation into a M2-like profile, and under inflammatory conditions induced by LPS treatment, inhibited HLA-DR upregulation by resting M0 macrophages, originated a similar percentage of TNF-<i>α</i>^＋ cells, and inhibited IL-10 secretion, similar to OW-ADSCs and BMSCs, which were used for comparison, as these are the main alternative cell types available for therapeutic purposes. Our results showed that Ex-Ob ADSCs mirrored OW-ADSCs in macrophage education, favoring the M2 immunophenotype and a mixed (M1/M2) secretory response. These results have translational potential, since they provide evidence that ADSCs from both Ex-Ob and OW subjects can be used in regenerative medicine in eligible therapies. Further <i>in vivo</i> studies will be fundamental to validate these observations.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"425-437"},"PeriodicalIF":2.3,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10686802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10103748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>In Vivo</i> Stem Cell Imaging Principles and Applications.","authors":"Seongje Hong, Dong-Sung Lee, Geun-Woo Bae, Juhyeong Jeon, Hak Kyun Kim, Siyeon Rhee, Kyung Oh Jung","doi":"10.15283/ijsc23045","DOIUrl":"10.15283/ijsc23045","url":null,"abstract":"<p><p>Stem cells are the foundational cells for every organ and tissue in our body. Cell-based therapeutics using stem cells in regenerative medicine have received attracting attention as a possible treatment for various diseases caused by congenital defects. Stem cells such as induced pluripotent stem cells (iPSCs) as well as embryonic stem cells (ESCs), mesenchymal stem cells (MSCs), and neuroprogenitors stem cells (NSCs) have recently been studied in various ways as a cell-based therapeutic agent. When various stem cells are transplanted into a living body, they can differentiate and perform complex functions. For stem cell transplantation, it is essential to determine the suitability of the stem cell-based treatment by evaluating the origin of stem, the route of administration, <i>in vivo</i> bio-distribution, transplanted cell survival, function, and mobility. Currently, these various stem cells are being imaged <i>in vivo</i> through various molecular imaging methods. Various imaging modalities such as optical imaging, magnetic resonance imaging (MRI), ultrasound (US), positron emission tomography (PET), and single-photon emission computed tomography (SPECT) have been introduced for the application of various stem cell imaging. In this review, we discuss the principles and recent advances of <i>in vivo</i> molecular imaging for application of stem cell research.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"363-375"},"PeriodicalIF":2.3,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10686800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10103744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptional Signature of Valproic Acid-Induced Neural Tube Defects in Human Spinal Cord Organoids.","authors":"Ju-Hyun Lee, Mohammed R Shaker, Si-Hyung Park, Woong Sun","doi":"10.15283/ijsc23012","DOIUrl":"10.15283/ijsc23012","url":null,"abstract":"<p><p>In vertebrates, the entire central nervous system is derived from the neural tube, which is formed through a conserved early developmental morphogenetic process called neurulation. Although the perturbations in neurulation caused by genetic or environmental factors lead to neural tube defects (NTDs), the most common congenital malformation and the precise molecular pathological cascades mediating NTDs are not well understood. Recently, we have developed human spinal cord organoids (hSCOs) that recapitulate some aspects of human neurulation and observed that valproic acid (VPA) could cause neurulation defects in an organoid model. In this study, we identified and verified the significant changes in cell-cell junctional genes/proteins in VPA-treated organoids using transcriptomic and immunostaining analysis. Furthermore, VPA-treated mouse embryos exhibited impaired gene expression and NTD phenotypes, similar to those observed in the hSCO model. Collectively, our data demonstrate that hSCOs provide a valuable biological resource for dissecting the molecular pathways underlying the currently unknown human neurulation process using destructive biological analysis tools.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"385-393"},"PeriodicalIF":2.3,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10686804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10112448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of Risks and Benefits of Using Antibiotics Resistance Genes in Mesenchymal Stem Cell-Based <i>Ex-Vivo</i> Therapy.","authors":"Narayan Bashyal, Young Jun Lee, Jin-Hwa Jung, Min Gyeong Kim, Kwang-Wook Lee, Woo Sup Hwang, Sung-Soo Kim, Da-Young Chang, Haeyoung Suh-Kim","doi":"10.15283/ijsc23053","DOIUrl":"10.15283/ijsc23053","url":null,"abstract":"<p><p>Recently, <i>ex-vivo</i> gene therapy has emerged as a promising approach to enhance the therapeutic potential of mesenchymal stem cells (MSCs) by introducing functional genes <i>in vitro</i>. Here, we explored the need of using selection markers to increase the gene delivery efficiency and evaluated the potential risks associated with their use in the manufacturing process. We used MSCs/CD that carry the cytosine deaminase gene (CD) as a therapeutic gene and a puromycin resistance gene (<i>PuroR</i>) as a selection marker. We evaluated the correlation between the therapeutic efficacy and the purity of therapeutic MSCs/CD by examining their anti-cancer effect on co-cultured U87/GFP cells. To simulate <i>in vivo</i> horizontal transfer of the <i>PuroR</i> gene <i>in vivo</i>, we generated a puromycin-resistant <i>E. coli</i> (<i>E. coli</i>/<i>PuroR</i>) by introducing the <i>PuroR</i> gene and assessed its responsiveness to various antibiotics. We found that the anti-cancer effect of MSCs/CD was directly proportional to their purity, suggesting the crucial role of the <i>PuroR</i> gene in eliminating impure unmodified MSCs and enhancing the purity of MSCs/CD during the manufacturing process. Additionally, we found that clinically available antibiotics were effective in inhibiting the growth of hypothetical microorganism, <i>E. coli</i>/<i>PuroR</i>. In summary, our study highlights the potential benefits of using the <i>PuroR</i> gene as a selection marker to enhance the purity and efficacy of therapeutic cells in MSC-based gene therapy. Furthermore, our study suggests that the potential risk of horizontal transfer of antibiotics resistance genes <i>in vivo</i> can be effectively managed by clinically available antibiotics.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"438-447"},"PeriodicalIF":2.3,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10686797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9690162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preclinical Study on Biodistribution of Mesenchymal Stem Cells after Local Transplantation into the Brain.","authors":"Narayan Bashyal, Min Gyeong Kim, Jin-Hwa Jung, Rakshya Acharya, Young Jun Lee, Woo Sup Hwang, Jung-Mi Choi, Da-Young Chang, Sung-Soo Kim, Haeyoung Suh-Kim","doi":"10.15283/ijsc23062","DOIUrl":"10.15283/ijsc23062","url":null,"abstract":"<p><p>Therapeutic efficacy of mesenchymal stem cells (MSCs) is determined by biodistribution and engraftment <i>in vivo</i>. Compared to intravenous infusion, biodistribution of locally transplanted MSCs are partially understood. Here, we performed a pharmacokinetics (PK) study of MSCs after local transplantation. We grafted human MSCs into the brains of immune-compromised nude mice. Then we extracted genomic DNA from brains, lungs, and livers after transplantation over a month. Using quantitative polymerase chain reaction with human Alu-specific primers, we analyzed biodistribution of the transplanted cells. To evaluate the role of residual immune response in the brain, MSCs expressing a cytosine deaminase (MSCs/CD) were used to ablate resident immune cells at the injection site. The majority of the Alu signals mostly remained at the injection site and decreased over a week, finally becoming undetectable after one month. Negligible signals were transiently detected in the lung and liver during the first week. Suppression of Iba1-positive microglia in the vicinity of the injection site using MSCs/CD prolonged the presence of the Alu signals. After local transplantation in xenograft animal models, human MSCs remain predominantly near the injection site for limited time without disseminating to other organs. Transplantation of human MSCs can locally elicit an immune response in immune compromised animals, and suppressing resident immune cells can prolong the presence of transplanted cells. Our study provides valuable insights into the <i>in vivo</i> fate of locally transplanted stem cells and a local delivery is effective to achieve desired dosages for neurological diseases.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"415-424"},"PeriodicalIF":2.3,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10686801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10109941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-Intensity Pulsed Ultrasound Promotes BMP9 Induced Osteoblastic Differentiation in Rat Dedifferentiated Fat Cells.","authors":"Fumiaki Setoguchi, Kotaro Sena, Kazuyuki Noguchi","doi":"10.15283/ijsc23027","DOIUrl":"10.15283/ijsc23027","url":null,"abstract":"<p><p>Dedifferentiated fat cells (DFATs) isolated from mature adipocytes have a multilineage differentiation capacity similar to mesenchymal stem cells and are considered as promising source of cells for tissue engineering. Bone morphogenetic protein 9 (BMP9) and low-intensity pulsed ultrasound (LIPUS) have been reported to stimulate bone formation both <i>in vitro</i> and <i>in vivo</i>. However, the combined effect of BMP9 and LIPUS on osteoblastic differentiation of DFATs has not been studied. After preparing DFATs from mature adipose tissue from rats, DFATs were treated with different doses of BMP9 and/or LIPUS. The effects on osteoblastic differentiation were assessed by changes in alkaline phosphatase (ALP) activity, mineralization/calcium deposition, and expression of bone related genes; Runx2, osterix, osteopontin. No significant differences for ALP activity, mineralization deposition, as well as expression for bone related genes were observed by LIPUS treatment alone while treatment with BMP9 induced osteoblastic differentiation of DFATs in a dose dependent manner. Further, co-treatment with BMP9 and LIPUS significantly increased osteoblastic differentiation of DFATs compared to those treated with BMP9 alone. In addition, upregulation for BMP9-receptor genes was observed by LIPUS treatment. Indomethacin, an inhibitor of prostaglandin synthesis, significantly inhibited the synergistic effect of BMP9 and LIPUS co-stimulation on osteoblastic differentiation of DFATs. LIPUS promotes BMP9 induced osteoblastic differentiation of DFATs <i>in vitro</i> and prostaglandins may be involved in this mechanism.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"406-414"},"PeriodicalIF":2.3,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10686803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9690160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parathyroid Hormone-Related Protein Promotes the Proliferation of Patient-Derived Glioblastoma Stem Cells via Activating cAMP/PKA Signaling Pathway.","authors":"Zhenyu Guo,&nbsp;Tingqin Huang,&nbsp;Yingfei Liu,&nbsp;Chongxiao Liu","doi":"10.15283/ijsc22097","DOIUrl":"https://doi.org/10.15283/ijsc22097","url":null,"abstract":"<p><strong>Background and objectives: </strong>Glioblastoma (GBM) is an aggressive primary brain tumor characterized by its heterogeneity and high recurrence and lethality rates. Glioblastoma stem cells (GSCs) play a crucial role in therapy resistance and tumor recurrence. Therefore, targeting GSCs is a key objective in developing effective treatments for GBM. The role of Parathyroid hormone-related peptide (PTHrP) in GBM and its impact on GSCs remains unclear. This study aimed to investigate the effect of PTHrP on GSCs and its potential as a therapeutic target for GBM.</p><p><strong>Methods and results: </strong>Using the Cancer Genome Atlas (TCGA) database, we found higher expression of PTHrP in GBM, which correlated inversely with survival. GSCs were established from three human GBM samples obtained after surgical resection. Exposure to recombinant human PTHrP protein (rPTHrP) at different concentrations significantly enhanced GSCs viability. Knockdown of PTHrP using target-specific siRNA (siPTHrP) inhibited tumorsphere formation and reduced the number of BrdU-positive cells. In an orthotopic xenograft mouse model, suppression of PTHrP expression led to significant inhibition of tumor growth. The addition of rPTHrP in the growth medium counteracted the antiproliferative effect of siPTHrP. Further investigation revealed that PTHrP increased cAMP concentration and activated the PKA signaling pathway. Treatment with forskolin, an adenylyl cyclase activator, nullified the antiproliferative effect of siPTHrP.</p><p><strong>Conclusions: </strong>Our findings demonstrate that PTHrP promotes the proliferation of patient-derived GSCs by activating the cAMP/PKA signaling pathway. These results uncover a novel role for PTHrP and suggest its potential as a therapeutic target for GBM treatment.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 3","pages":"315-325"},"PeriodicalIF":2.3,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7f/9f/ijsc-16-3-315.PMC10465338.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10124843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Applications of Bioinspired Platforms for Enhancing Immunomodulatory Function of Mesenchymal Stromal Cells.","authors":"Ok-Hyeon Kim,&nbsp;Tae Jin Jeon,&nbsp;Young In So,&nbsp;Yong Kyoo Shin,&nbsp;Hyun Jung Lee","doi":"10.15283/ijsc22211","DOIUrl":"https://doi.org/10.15283/ijsc22211","url":null,"abstract":"<p><p>Mesenchymal stromal cells (MSCs) have attracted scientific and medical interest due to their self-renewing properties, pluripotency, and paracrine function. However, one of the main limitations to the clinical application of MSCs is their loss of efficacy after transplantation <i>in vivo</i>. Various bioengineering technologies to provide stem cell niche-like conditions have the potential to overcome this limitation. Here, focusing on the stem cell niche microenvironment, studies to maximize the immunomodulatory potential of MSCs by controlling biomechanical stimuli, including shear stress, hydrostatic pressure, stretch, and biophysical cues, such as extracellular matrix mimetic substrates, are discussed. The application of biomechanical forces or biophysical cues to the stem cell microenvironment will be beneficial for enhancing the immunomodulatory function of MSCs during cultivation and overcoming the current limitations of MSC therapy.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 3","pages":"251-259"},"PeriodicalIF":2.3,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a4/11/ijsc-16-3-251.PMC10465339.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10124844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dissection of Cellular Communication between Human Primary Osteoblasts and Bone Marrow Mesenchymal Stem Cells in Osteoarthritis at Single-Cell Resolution.","authors":"Ying Liu, Yan Chen, Xiao-Hua Li, Chong Cao, Hui-Xi Zhang, Cui Zhou, Yu Chen, Yun Gong, Jun-Xiao Yang, Liang Cheng, Xiang-Ding Chen, Hui Shen, Hong-Mei Xiao, Li-Jun Tan, Hong-Wen Deng","doi":"10.15283/ijsc22101","DOIUrl":"10.15283/ijsc22101","url":null,"abstract":"<p><strong>Background and objectives: </strong>Osteoblasts are derived from bone marrow mesenchymal stem cells (BMMSCs) and play important role in bone remodeling. While our previous studies have investigated the cell subtypes and heterogeneity in osteoblasts and BMMSCs separately, cell-to-cell communications between osteoblasts and BMMSCs <i>in vivo</i> in humans have not been characterized. The aim of this study was to investigate the cellular communication between human primary osteoblasts and bone marrow mesenchymal stem cells.</p><p><strong>Methods and results: </strong>To investigate the cell-to-cell communications between osteoblasts and BMMSCs and identify new cell subtypes, we performed a systematic integration analysis with our single-cell RNA sequencing (scRNA-seq) transcriptomes data from BMMSCs and osteoblasts. We successfully identified a novel preosteoblasts subtype which highly expressed ATF3, CCL2, CXCL2 and IRF1. Biological functional annotations of the transcriptomes suggested that the novel preosteoblasts subtype may inhibit osteoblasts differentiation, maintain cells to a less differentiated status and recruit osteoclasts. Ligand-receptor interaction analysis showed strong interaction between mature osteoblasts and BMMSCs. Meanwhile, we found <i>FZD1</i> was highly expressed in BMMSCs of osteogenic differentiation direction. WIF1 and <i>SFRP4</i>, which were highly expressed in mature osteoblasts were reported to inhibit osteogenic differentiation. We speculated that WIF1 and sFRP4 expressed in mature osteoblasts inhibited the binding of FZD1 to Wnt ligand in BMMSCs, thereby further inhibiting osteogenic differentiation of BMMSCs.</p><p><strong>Conclusions: </strong>Our study provided a more systematic and comprehensive understanding of the heterogeneity of osteogenic cells. At the single cell level, this study provided insights into the cell-to-cell communications between BMMSCs and osteoblasts and mature osteoblasts may mediate negative feedback regulation of osteogenesis process.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 3","pages":"342-355"},"PeriodicalIF":2.3,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3a/76/ijsc-16-3-342.PMC10465330.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10124281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}