Jiqin Zhou, Wei Ni, Yating Ling, Xiaorui Lv, Dongdong Niu, Yu Zeng, Yun Qiu, Y. Si, Ziyu Wang, Jiabo Hu
{"title":"Human neural stem cells secretome inhibits lipopolysaccharide-induced neuroinflammation through modulating microglia polarization by activating PPAR-γ.","authors":"Jiqin Zhou, Wei Ni, Yating Ling, Xiaorui Lv, Dongdong Niu, Yu Zeng, Yun Qiu, Y. Si, Ziyu Wang, Jiabo Hu","doi":"10.1089/scd.2022.0081","DOIUrl":"https://doi.org/10.1089/scd.2022.0081","url":null,"abstract":"Neuroinflammation is one of the typical events in multiple neurodegenerative diseases, whereas microglia are the critical participants in the pathogenesis of neuroinflammation. Several studies suggest that neural stem cells (NSCs) present immunomodulatory benefits due to their paracrine products, which contain mounting trophic factors. In the current study, the anti-inflammatory effects of neural stem cells secretome (NSC-S) on lipopolysaccharide (LPS)-induced neuroinflammatory models were evaluated in vivo and the underlying mechanism was further investigated in vitro. It was revealed that NSC-S significantly attenuated the severity of LPS-induced behaviour disorders and inflammatory response in mice. In vitro studies found that NSC-S significantly promoted the polarization of microglia from proinflammatory M1 to anti-inflammatory M2 phenotype, and reduced the production of proinflammatory cytokines while elevated anti-inflammatory cytokines in BV2 cells. NSC-S promoted peroxisome proliferator-activated receptor gamma (PPAR-γ) pathway activation. However, these effects of NSC-S were abrogated by PPAR-γ inhibitor GW9662. Notably, the fatty acid binding protein 5 (FABP5) in NSC-S may mediate PPAR-γ activation and inflammation remission. In summary, NSC-S promotes the regression of LPS-induced microglia-mediated inflammation through the PPAR-γ pathway. This function might be achieved via FABP5.","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2022-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43742417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maria Espinosa Gonzalez, Lisa D. Volk-Draper, Nihit Bhattarai, A. Wilber, S. Ran
{"title":"Th2 Cytokines IL-4, IL-13, and IL-10 Promote Differentiation of Pro-Lymphatic Progenitors Derived from Bone Marrow Myeloid Precursors","authors":"Maria Espinosa Gonzalez, Lisa D. Volk-Draper, Nihit Bhattarai, A. Wilber, S. Ran","doi":"10.1089/scd.2022.0004","DOIUrl":"https://doi.org/10.1089/scd.2022.0004","url":null,"abstract":"Myeloid-lymphatic endothelial cell progenitors (M-LECP) are a subset of bone marrow (BM)-derived cells characterized by expression of M2-type macrophage markers. We previously showed significant contribution of M-LECP to tumor lymphatic formation and metastasis in human clinical breast tumors and corresponding mouse models. Since M2 type is induced in macrophages by immunosuppressive Th2 cytokines IL-4, IL-13, and IL-10, we hypothesized that these factors might promote pro-lymphatic specification of M-LECP during their differentiation from BM myeloid precursors. To test this hypothesis, we analyzed expression of Th2 cytokines and their receptors in mouse BM cells under conditions leading to M-LECP differentiation, namely, CSF-1 treatment followed by activation of TLR4. We found that under these conditions, all three Th2 receptors were strongly upregulated in >95% of the cells that also secrete endogenous IL-10, but not IL-4 or IL-13 ligands. However, addition of any of the Th2 factors to CSF-1 primed cells significantly increased generation of myeloid-lymphatic progenitors as indicated by co-induction of lymphatic-specific (eg, Lyve-1, integrin-a9, collectin-12, and stabilin-1) and M2-type markers (eg, CD163, CD204, CD206, and PD-L1). Antibody-mediated blockade of either IL-10 receptor (IL-10R) or IL-10 ligand significantly reduced both immunosuppressive and lymphatic phenotypes. Moreover, tumor-recruited Lyve-1+ lymphatic progenitors in vivo expressed all Th2 receptors as well as corresponding ligands, including IL-4 and IL-13, which were absent in BM cells. This study presents original evidence for the significant role of Th2 cytokines in co-development of immunosuppressive and lymphatic phenotypes in tumor-recruited M2-type myeloid cells. Progenitor-mediated increase in lymphatic vessels can enhance immunosuppression by physical removal of stimulatory immune cells. Thus, targeting Th2 pathways might simultaneously relieve immunosuppression and inhibit differentiation of pro-lymphatic progenitors that ultimately promote tumor spread.","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":"31 1","pages":"322 - 333"},"PeriodicalIF":4.0,"publicationDate":"2022-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46409414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L. Kokai, Joseph Chen, Dong Wang, Sheri Wang, F. Egro, Benjamin K. Schilling, Hengyun Sun, A. Ejaz, J. P. Rubin, Jeffrey A. Gusenoff, N. Vo, K. Onishi, G. Sowa
{"title":"Comparison of Clinically Relevant Adipose Preparations on Articular Chondrocyte Phenotype in a Novel In Vitro Co-Culture Model.","authors":"L. Kokai, Joseph Chen, Dong Wang, Sheri Wang, F. Egro, Benjamin K. Schilling, Hengyun Sun, A. Ejaz, J. P. Rubin, Jeffrey A. Gusenoff, N. Vo, K. Onishi, G. Sowa","doi":"10.1089/scd.2021.0355","DOIUrl":"https://doi.org/10.1089/scd.2021.0355","url":null,"abstract":"Adipose therapeutics, including isolated cell fractions and tissue emulsifications, have been explored for osteoarthritis (OA) treatment, however the optimal preparation method and bioactive tissue component for healing has yet to be determined. This in-vitro study compared the effects of adipose preparations on cultured knee chondrocytes. De-identified human articular chondrocytes were co-cultured with adipose preparations for 36 or 72 hours. Human adipose tissues were obtained from abdominal panniculectomy procedures and processed using three different techniques: enzymatic digestion to release stromal vascular fraction (SVF), emulsification with luer-to-luer transfer (nanofat), and processing in a bead-mill (Lipogems, Lipogems International SpA, Milan, Italy). Gene expression in both chondrocytes and adipose preparations was measured to assess cellular inflammation, catabolism, and anabolism. Results demonstrated that chondrocytes cultured with SVF consistently showed increased inflammatory and catabolic gene expression compared to control chondrocytes at both 36-and 72-hour timepoints. Alternatively, chondrocytes co-cultured with either nanofat or bead-mill processed adipose derivatives yielded minimal pro-inflammatory effects and instead increased anabolism and regeneration of cartilage extracellular matrix. Interestingly, nanofat preparations induced transient matrix anabolism while Lipogems adipose consistently demonstrated increased matrix synthesis at both study time points following co-culture. This evaluation of the regenerative potential of adipose-derived preparations as a clinical tool for knee OA treatment suggests that mechanically processed preparations may be more efficacious than an isolated SVF cell preparation.","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2022-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48405514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Reema Fadoul, Tharwat Haj Khalil, Idan Redenski, D. Oren, Asaf Zigron, A. Sharon, A. Dror, M. Falah, S. Srouji
{"title":"The Modulatory Effect of Adipose-Derived Stem Cells on Endometrial Polyp Fibroblasts.","authors":"Reema Fadoul, Tharwat Haj Khalil, Idan Redenski, D. Oren, Asaf Zigron, A. Sharon, A. Dror, M. Falah, S. Srouji","doi":"10.1089/scd.2021.0273","DOIUrl":"https://doi.org/10.1089/scd.2021.0273","url":null,"abstract":"Endometrial polyps (EPs) are benign overgrowths of the endometrium, with the potential to cause severe complications, ranging from discomfort to inflammation and infertility. Dysfunction of endometrial fibroblasts may be a critical component leading to the development of polyps. While surgical intervention is the common remedy for severe cases, it comes with drawbacks, including infection, bleeding, and risk of damage to the cervix and adjacent tissues. Adipose-derived mesenchymal stromal cells (ASCs) are at the focus of modern medicine, as key modulators of tissue homeostasis, inflammation and tissue repair, rendering them prime candidate agents for tissue regeneration and cell-based therapies. In the current work, endometrial polyps were isolated from patients admitted to the OB/GYN department at the Galilee Medical Center and extracted fibroblasts (EPFs) were isolated and characterized. ASCs were isolated from healthy patients. The effect of EPF- and ASC-conditioned media (CM) on polyp-derived fibroblasts was evaluated, in both 2D and 3D assays, as well as on the expression of matrix-related gene expression. Herein, EPFs exposed to ASC-CM exhibited reduced migration, invasion, contraction of hydrogels, and extracellular matrix deposition, compared to those exposed to EPF-CM. Altogether, the current work suggests that ASCs may have a modulating effect on fibroblasts involved in forming endometrial polyps and may serve as the basis for conservative treatment strategies aimed at treating severe cases of EPs.","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2022-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42903089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Rapid conversion of human induced pluripotent stem cells into dopaminergic neurons by inducible expression of two transcription factors.","authors":"Kaneyasu Nishimura, T. Nitta, K. Doi, K. Takata","doi":"10.1089/scd.2021.0363","DOIUrl":"https://doi.org/10.1089/scd.2021.0363","url":null,"abstract":"Human pluripotent stem cells (hPSCs) including human embryonic stem cells and human induced pluripotent stem cells (hiPSCs) provide promising sources for regenerative therapy, disease modeling, and drug screening. Relevant efforts have been invested in establishing robust induction protocols for PSC-derived dopaminergic (DA) neuron generation by mimicking brain development-related signaling pathways. However, these protocols require fully trained techniques and a long time to yield mature DA neurons. In this study, to accelerate the entire process, we generated a hiPSC line differentiating into DA neurons by the inducible force expression of two transcription factors ASCL1 and LMX1A. Using this hiPSC line, we established a rapid and simple induction protocol to generate mature DA neurons in 28 days. The induced DA neurons were characterized by gene expression and immunohistochemical analyses of fundamental DA neuronal markers. Moreover, the cell functional properties were analyzed by a multielectrode array system on day 28. This resource offers future applications for high-throughput screening, such as drug development and toxicology that require highly validated DA neurons.","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2022-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49149076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yingfei Liu, Y. Luan, K. Ma, Zhichao Zhang, Yong Liu, Xinlin Chen
{"title":"ISL1 promotes human glioblastoma-derived stem cells self-renewal by activation of SHH/GLI1 function.","authors":"Yingfei Liu, Y. Luan, K. Ma, Zhichao Zhang, Yong Liu, Xinlin Chen","doi":"10.1089/scd.2021.0344","DOIUrl":"https://doi.org/10.1089/scd.2021.0344","url":null,"abstract":"Glioblastoma, the most aggressive primary heterogeneous primary brain tumor, is a glioma subtype of glioma that originates from the glial cells of the central nervous system. Glioblastoma stem cells (GSCs), situated at the top of the hierarchy, initiate and maintain the tumor and are largely accountable for glioblastoma resistance to the mainstay treatment and recurrence. The LIM homeobox transcription factor islet1(ISL1) induces tumorigenicity in various tumors; however, its function in GSCs has been less reported. We aimed to generate GSCs from surgical specimens of human glioblastoma and investigate the effect of ISL1 knockdown on GSCs. We established patient derived GSCs, determined cancer stem cell marker expression, and immunostained GSCs to assess cell viability and apoptosis. We demonstrated that ISL1 deletion decreased the GSC viability and proliferation, and upregulated apoptosis. Moreover, we performed enzyme-linked immunosorbent assay and western blotting and found that ISL1 knockdown affected the expression of sonic hedgehog (SHH) and its downstream regulator GLI1, and further validated these results by supplementing the cells with recombinant SHH. Our results suggested that ISL1 played a critical role in regulating GBM growth and that an ISL1/SHH/GLI1 pathway was required for the maintenance of GBM progression and malignancy. The regulation of GSC growth via ISL1 might be a mechanism of interest for future therapeutic studies.","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2022-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49537588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yu Zhou, Robert R A Wilson, Abinav Udaiyar, J. McLemore, H. Sadri-Ardekani, T. Criswell
{"title":"Pituitary lineage differentiation from human-induced pluripotent stem cells in 2D and 3D cultures.","authors":"Yu Zhou, Robert R A Wilson, Abinav Udaiyar, J. McLemore, H. Sadri-Ardekani, T. Criswell","doi":"10.1089/scd.2021.0354","DOIUrl":"https://doi.org/10.1089/scd.2021.0354","url":null,"abstract":"Despite its small size, the pituitary gland plays a central role in the maintenance of normal homeostasis of most physiological systems through its regulation of the function of other endocrine glands. The complexity of the anterior pituitary gland, due to its composition of several different hormone-secreting cell types, begets a plethora of disorders and pathologies due primarily to hypo- or hyper-secretion of hormones. The gonadotrophs, which make up less than 5% of the total number of cells in the anterior pituitary, serve to regulate gonad development and sexual reproduction in males and females. Despite the increased research on the development of models to study pituitary function within the last decade, a model specifically designed to study the gonadotrophs is still lacking. The development of organoid technology has facilitated research in the field of personalized medicine and physiological testing using patient-derived cells. The ability to produce pituitary organoids would allow researchers to construct an in vitro model of the human hypothalamic-pituitary-gonadal (HPG) or -adrenal (HPA) axis to use in further fertility or endocrine research. The application of this technology in patients could revolutionize the treatment of infertility and a variety of neuroendocrine disorders. The impetus behind this stud was to develop a pituitary-like organoid consisting only of gonadotrophs. Despite the lack of success in differentiating gonadotrophs, pituitary-like organoids were differentiated from human-induced pluripotent stem cells. In addition, 2D and 3D differentiated cultures were characterized and compared to human adult cadaveric pituitary tissue.","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2022-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47224050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Femke Christina Ching-Chuan van Rhijn-Brouwer, Hendrik Gremmels, Krista Den Ouden, Martin Teraa, Joost Ougust Fledderus, Marianne Christina Verhaar
{"title":"Human Bone Marrow Mononuclear Cells Do Not Improve Limb Perfusion in the Hindlimb Ischemia Model.","authors":"Femke Christina Ching-Chuan van Rhijn-Brouwer, Hendrik Gremmels, Krista Den Ouden, Martin Teraa, Joost Ougust Fledderus, Marianne Christina Verhaar","doi":"10.1089/scd.2021.0261","DOIUrl":"https://doi.org/10.1089/scd.2021.0261","url":null,"abstract":"<p><p>Effective treatments for chronic limb-threatening ischemia are lacking. (Pre)clinical studies on administration of bone marrow (BM) mononuclear cells (MNCs) and BM-derived mesenchymal stromal cells (MSCs) have shown variable results and no studies have directly compared administration of human BM MNCs and BM MSCs in in vivo models. We studied the effect of intramuscular administration of human BM-derived MNCs and MSCs on limb perfusion in the murine hindlimb ischemia (HLI) model. Human BM MNCs and MSCs were obtained from healthy consenting donors. Both cell types were cryopreserved before use. Twenty-four hours after induction of HLI, nude NMRI mice were randomized to receive intramuscular administration of human BM MNCs (<i>n</i> = 13), or BM MSCs (<i>n</i> = 14), or vehicle control (<i>n</i> = 19) in various doses. Limb perfusion was measured using laser Doppler imaging on day 0, 1, 4, 7, 10, and 14. Intramuscular injection of human BM MNCs did not improve limb perfusion as compared with vehicle over the 2 weeks after cell administration (<i>P</i> = 0.88, mean relative perfusion for vehicle 0.56 ± 0.04 and 0.53 ± 0.04 for BM MNCs at day 14). Administration of human BM MSCs significantly improved limb perfusion as compared with both BM MNCs and vehicle (<i>P</i> ≤ 0.001, mean relative perfusion at day 14 0.79 ± 0.06). Our data suggest that BM MNCs are less suitable than BM MSCs for cell-based therapy that aims to restore perfusion.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":"31 7-8","pages":"176-180"},"PeriodicalIF":4.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/26/0b/scd.2021.0261.PMC9057881.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39913390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lidi Deng, Siqi Yi, Xiaohui Yin, Yang Li, Qingxian Luan
{"title":"Downregulating <i>MFN2</i> Promotes the Differentiation of Induced Pluripotent Stem Cells into Mesenchymal Stem Cells through the PI3K/Akt/GSK-3β/Wnt Signaling Pathway.","authors":"Lidi Deng, Siqi Yi, Xiaohui Yin, Yang Li, Qingxian Luan","doi":"10.1089/scd.2021.0316","DOIUrl":"https://doi.org/10.1089/scd.2021.0316","url":null,"abstract":"<p><p>Understanding the mechanism of the differentiation of induced pluripotent stem cells (iPSCs) into mesenchymal stem cells (MSCs) and promoting the production efficiency of iPSC-derived MSCs (iPSC-MSCs) are critical to periodontal tissue engineering. However, the gene networks that control this differentiation process from iPSCs into MSCs are poorly understood. We demonstrated that <i>MFN2</i> knockdown showed a positive effect on the triploblastic and MSC differentiation from iPSCs. Activation of the PI3K/Akt signaling pathway by <i>MFN2</i> knockdown activated the Wnt/β-catenin signaling pathway by inhibiting GSK-3β and reducing β-catenin degradation. Inhibitor of the PI3K/Akt signaling pathway normalized the enhanced efficiency of differentiation into MSCs of <i>MFN2</i>-KD iPSCs and Wnt activator-treated control iPSCs. <i>MFN2</i>-OE iPSCs displayed an opposite phenotype. In conclusion, downregulating <i>MFN2</i> promotes the differentiation of iPSCs into MSCs by activating the PI3K/Akt/GSK-3β/Wnt signaling pathway. Our results reveal a crucial function and mechanism for <i>MFN2</i> in regulating MSC differentiation from iPSCs, which will provide new ideas for periodontal tissue engineering and periodontal regenerative treatment by using iPSC-MSCs.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":"31 7-8","pages":"181-194"},"PeriodicalIF":4.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39743440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L. Ni, Huaizhou You, Mengjing Wang, Jing Qian, Jing Chen
{"title":"BrdU Methodology for Labeling Renal Stem Cells during Kidney Development of Mice.","authors":"L. Ni, Huaizhou You, Mengjing Wang, Jing Qian, Jing Chen","doi":"10.1089/scd.2021.0362","DOIUrl":"https://doi.org/10.1089/scd.2021.0362","url":null,"abstract":"A continuous Bromodeoxyuridine (BrdU) labeling approach was used during the whole process of the mice kidney development to explore the best BrdU-labeling time, the distribution of BrdU-retaining cells, and to probe into the niche of stem cells in adult kidney. BrdU were injected intraperitoneally to the mice once daily for 3 consecutive days from day 11.5 of embryonic period (E11.5) until the postnatal day 21.5 (P21.5). The kidneys were harvested 24 hours after the last BrdU injection and 6 months of age. A renal injury model of subtotal nephrectomy (Nx) in adult mice treated with BrdU was used to observe the response of BrdU-retaining cells to renal injury. When BrdU labeled at E11.5-13.5, the BrdU-retaining cells were mainly detected in the papilla and inner medulla in adult mice. When BrdU labeled at P0.5-11.5, the BrdU-retaining cells were mainly detected in the inner medulla and outer medulla. When BrdU labeled at P12.5-17.5, the BrdU-retaining cells were mainly detected in the outer medulla. When BrdU labeled at P18.5-21.5, almost no BrdU-positive cells could be found, except the cortex. 72 hours after Nx operation in adult mice by BrdU-labeling at P0.5-2.5 or P15.5-17.5, a significant increase of BrdU-retaining cells was found in many cortical proximal tubules, while a dramatic decrease was detected in medulla near the incision edge. Moreover, most of BrdU-positive cells were not co-stained with proliferating cell nuclear antigen (PCNA). The distributions of label-retaining cells in the mice kidney were different if BrdU was administered in different periods of kidney development. Most of BrdU-retaining cells were quiescent, the proximal tubules were the only segments that always contained BrdU positive cells, which may have the niche of stem cells in adult kidney.","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2022-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47310334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}