Stem cells and development最新文献

{"title":"Cell Surface Accumulation of Intracellular Leucine Proline-Enriched Proteoglycan 1 Enhances Odontogenic Potential of Human Dental Pulp Stem Cells.","authors":"Kyung-Jung Kang,&nbsp;Min-Jeong Choi,&nbsp;Tae-Jun Min,&nbsp;Tae Min You,&nbsp;Gyutae Lee,&nbsp;Seon-Yle Ko,&nbsp;Young-Joo Jang","doi":"10.1089/scd.2022.0174","DOIUrl":"https://doi.org/10.1089/scd.2022.0174","url":null,"abstract":"<p><p>Primary dental pulp cells can be differentiated into odontoblast-like cells, which are responsible for dentin formation and mineralization. Successful differentiation of primary dental pulp cells can be verified using a few markers. However, odontoblast-specific cell surface markers have not been fully studied yet. LEucine PRoline-Enriched Proteoglycan 1 (LEPRE1) is a basement membrane-associated proteoglycan. LEPRE1 protein levels are increased during odontoblastic differentiation of human dental pulp cells (hDPCs). Intracellular and cell surface accumulation of this protein completely disappeared during dentin maturation and mineralization. Cell surface binding of an anti-LEPRE1 monoclonal antibody that could recognize an extracellular region was gradually increased in the odontoblastic stage. Overexpression and knockdown experiments showed that accumulation of intracellular LEPRE1 could lead to inefficient odontoblastic differentiation and that the movement of LEPRE1 from intracellular region to the cell surface was required for odontoblastic differentiation. Indeed, when LEPRE1 already located on the cell surface was blocked by the anti-LEPRE1 monoclonal antibody, odontoblastic differentiation of hDPCs was inhibited. In this study, we looked at other aspects of LEPRE1 function as a cell surface molecule rather than its known intracellular hydroxylase activity. Our results indicate that this protein has potential as a specific cell surface marker in odontoblastic differentiation.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":"31 21-22","pages":"684-695"},"PeriodicalIF":4.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10341056","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":"Proteomic Analysis of Retinal Conditioned Medium: The Effect on Early Differentiation of Embryonic Stem Cells into Retina.","authors":"Shudi Mao,&nbsp;Aiwen Miao,&nbsp;Yamei Cui,&nbsp;Jing Lu,&nbsp;Jianying Pan,&nbsp;Yishen Wang,&nbsp;Yiwen Hong,&nbsp;Yan Luo","doi":"10.1089/scd.2022.0067","DOIUrl":"https://doi.org/10.1089/scd.2022.0067","url":null,"abstract":"<p><p>Stem cell replacement therapy has emerged as one of the most promising treatment options for retinal degenerative diseases, which are the main causes of irreversible vision loss. Three-dimensional (3D) retinal organoid culture is a cutting-edge technology for differentiating embryonic stem cells into retinal cells by forming a laminated retinal structure. However, 3D culture systems have strict requirements with respect to the experimental environment and culture technologies. Our study aimed to investigate the effect of retinal conditioned medium (RCM) at different developmental stages on the early differentiation of embryonic stem cells into retina in a 3D culture system. In this study, we added RCM to the 3D culture system and found that it could promote the differentiation of mouse embryonic stem cells (mESCs) into neuroretina. We further explored the possible mechanisms of RCM that regulate differentiation through proteomic analysis. RCM at different time points disclosed different protein profiles. Proteins which improved energy metabolism of mESCs might help improve the viability of embryonic bodies. We then screened out <i>Snap25</i>, <i>Cntn1</i>, <i>Negr1</i>, <i>Dpysl2</i>, <i>Dpysl3</i>, and <i>Crmp1</i> as candidate proteins that might play roles in the differentiation and neurogenesis processes of mESCs, hoping to provide a basis for optimizing a retinal differentiation protocol from embryonic stem cells.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":"31 21-22","pages":"730-740"},"PeriodicalIF":4.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10689859","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":"Survival Motor Neuron Enhances Pluripotent Gene Expression and Facilitates Cell Reprogramming.","authors":"Wei-Fang Chang,&nbsp;Tzu-Ying Lin,&nbsp;Min Peng,&nbsp;Chia-Chun Chang,&nbsp;Jie Xu,&nbsp;Hsiu-Mei Hsieh-Li,&nbsp;Ji-Long Liu,&nbsp;Li-Ying Sung","doi":"10.1089/scd.2022.0091","DOIUrl":"https://doi.org/10.1089/scd.2022.0091","url":null,"abstract":"<p><p>Survival motor neuron (SMN) plays important roles in snRNP assembly and mRNA splicing. Deficiency of SMN causes spinal muscular atrophy (SMA), a leading genetic disease causing childhood mortality. Previous studies have shown that SMN regulates stem cell self-renewal and pluripotency in <i>Drosophila</i> and mouse and is abundantly expressed in mouse embryonic stem cells. However, whether SMN is required for establishment of pluripotency is unclear. In this study, we show that SMN is gradually upregulated in preimplantation mouse embryos and cultured cells undergoing cell reprogramming. Ectopic expression of SMN increased cell reprogramming efficiency, whereas knockdown of SMN impeded induced pluripotent stem cell (iPSC) colony formation. iPSCs could be derived from SMA model mice, but impairment in differentiation capacity may be present. The ectopic overexpression of SMN in iPSCs can upregulate the expression levels of some pluripotent genes and restore the neuronal differentiation capacity of SMA-iPSCs. Taken together, our findings not only demonstrate the functional relevance of SMN in establishment of cell pluripotency but also propose its potential application in facilitating iPSC derivation.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":"31 21-22","pages":"696-705"},"PeriodicalIF":4.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10339396","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":"Type 2 Diabetes Mellitus Promotes the Differentiation of Adipose Tissue-Derived Mesenchymal Stem Cells into Cancer-Associated Fibroblasts, Induced by Breast Cancer Cells.","authors":"Yun-Hsuan Chang,&nbsp;Nhat-Hoang Ngo,&nbsp;Cat-Khanh Vuong,&nbsp;Toshiharu Yamashita,&nbsp;Motoo Osaka,&nbsp;Yuji Hiramatsu,&nbsp;Osamu Ohneda","doi":"10.1089/scd.2022.0086","DOIUrl":"https://doi.org/10.1089/scd.2022.0086","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is a highly aggressive and invasive type of breast cancer. In addition, type 2 diabetes mellitus (T2DM) is recognized as a risk factor for cancer metastasis, which is associated with mortality in patients with breast cancer. Cancer-associated fibroblasts (CAFs) generated from adipose tissue-derived mesenchymal stem cells (AT-MSCs) play a vital role in the progression of TNBC. However, to date, whether T2DM affects the ability of AT-MSCs to differentiate into CAFs is still unclear. In this study, we found that in coculture with TNBC cells [breast cancer cells (BCCs)] under hypoxic conditions, AT-MSCs derived from T2DM donors (dAT-MSCs) were facilitated to differentiate into CAFs, which showed fibroblastic morphology and the induced expression of fibroblastic markers, such as fibroblast activation protein, fibroblast-specific protein, and vimentin. This was involved in the higher expression of transforming growth factor beta receptor 2 (TGFβR2) and the phosphorylation of Smad2/3. Furthermore, T2DM affected the fate and functions of CAFs derived from dAT-MSCs. While CAFs derived from AT-MSCs of healthy donors (AT-CAFs) exhibited the markers of inflammatory CAFs, those derived from dAT-MSCs (dAT-CAFs) showed the markers of myofibroblastic CAFs. Of note, in comparison with AT-CAFs, dAT-CAFs showed a higher ability to induce the proliferation and in vivo metastasis of BCCs, which was involved in the activation of the transforming growth factor beta (TGFβ)-Smad2/3 signaling pathway. Collectively, our study suggests that T2DM contributes to metastasis of BCCs by inducing the myofibroblastic CAFs differentiation of dAT-MSCs. In addition, targeting the TGFβ-Smad2/3 signaling pathway in dAT-MSCs may be useful in cancer therapy for TNBC patients with T2DM.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":"31 21-22","pages":"659-671"},"PeriodicalIF":4.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10401368","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":"The Dark Side of Adipose-Derived Mesenchymal Stromal Cells in Cutaneous Oncology: Roles, Expectations, and Potential Pitfalls.","authors":"Alessia Paganelli,&nbsp;Elena Rossi,&nbsp;Cristina Magnoni","doi":"10.1089/scd.2022.0189","DOIUrl":"https://doi.org/10.1089/scd.2022.0189","url":null,"abstract":"<p><p>Adipose-derived stromal cells (ADSCs) have well-established regenerative and immunomodulatory properties. For such reasons, ADSCs are currently under investigation for their use in the setting of both regenerative medicine and autoimmune diseases. As per dermatological disorders, mesenchymal stromal cell (MSC)-based strategies represent potential therapeutic tools not only for chronic ulcers and wound healing, but also for immune-mediated dermatoses. However, a growing body of research has been focusing on the role of MSCs in human cancers, due to the potential oncological risk of using MSC-based strategies linked to their antiapoptotic, proangiogenic, and immunosuppressive properties. In the dermatological setting, ADSCs have shown not only to promote melanoma growth and invasiveness, but also to induce drug resistance. In contrast, genetically modified ADSCs have been demonstrated to efficiently target therapies at tumor sites, due to their migratory properties and their peculiar tropism for cancer microenvironment. The present review briefly summarizes the findings published so far on the use of ADSCs in the dermato-oncological setting, with the majority of data being available for melanoma.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":" ","pages":"593-603"},"PeriodicalIF":4.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40353381","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":"Cerebral Organoids to Study Central Mechanisms of Pain: The Effect of Stem Cell Secretome on Opioid Receptors and Neuroplasticity.","authors":"Aline M Fernandes,&nbsp;Jonas Campos,&nbsp;Deolinda Silva,&nbsp;Sandra Barata Antunes,&nbsp;Rui Lima,&nbsp;Claudio Coelho,&nbsp;Ana M Marote,&nbsp;Hugo Leite-Almeida,&nbsp;Nuno Silva,&nbsp;António J Salgado","doi":"10.1089/scd.2022.0116","DOIUrl":"https://doi.org/10.1089/scd.2022.0116","url":null,"abstract":"<p><p>Over 90% of chronic pain (CP) patients receive opioids-based treatments, which led to a public health crisis with lasting impacts on social and economic wellbeing based on opioid addiction. Opioids act through activation of μ (MOR), δ (DOR), and κ (KOR) opioid receptors, which are broadly and differentially distributed throughout the brain. Chronic opioid consumption leads to brain changes such as alterations on neurotransmission, dendritic branching, and spine density, as well as an increase in apoptosis. To overcome opioid-related issues, extensive efforts have been made to search for an alternative treatment. Bioactive molecules secreted by stem cells, collectively known as secretome, have shown a positive impact in different pain models. However, there is a lack of studies on the role of secretome in modulating opioid receptors. By using cerebral organoids (CeO), a self-organized, functional, and multicellular 3D structure that resemble the brain, we were able to identify MOR, DOR, and KOR at different stages of maturation. Treatment with secretome increased MOR expression highlighting a possible role in pain signaling mechanisms. Opioid treatments did not impact the expression of neuronal maturation markers but together with secretome, they increased astrogliogenesis. Opioid-treated organoids presented higher dopamine secretion recapitulating an important physiological event after opioid exposure. This work demonstrates that CeO is an important model system for the study of opioid signaling with potential implications to the understanding of basic mechanisms related to pain physiology.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":" ","pages":"641-657"},"PeriodicalIF":4.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33455072","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":"Adipose-Derived Stromal/Stem Cell Response to Tumors and Wounds: Evaluation of Patient Age.","authors":"Katie M Hamel,&nbsp;Kara Q Liimatta,&nbsp;Jorge A Belgodere,&nbsp;Bruce A Bunnell,&nbsp;Jeffrey M Gimble,&nbsp;Elizabeth C Martin","doi":"10.1089/scd.2021.0280","DOIUrl":"10.1089/scd.2021.0280","url":null,"abstract":"<p><p>Tumors were characterized as nonhealing wounds by Virchow in 1858 and Dvorak in 1986. Since then, researchers have analyzed tumors from a new perspective. The parallels between tumorigenesis and physiological wound healing can provide a new framework for developing antitumor therapeutics. One commonality between tumors and wounds is the involvement of the stromal environment, particularly adipose stromal/stem cells (ASCs). ASCs exhibit dual functions, in which they stimulate tumor progression and assist in tissue repair and regeneration. Numerous studies have focused on the role of ASCs in cancer and wound healing, but none to date has linked age, cancer, and wound healing. Furthermore, very few studies have focused on the role of donor-specific characteristics of ASCs, such as age and their role in facilitating ASC behavior in cancer and wound healing. This review article is designed to provide important insights into the impact of donor age on ASC tumor and wound response and their role in facilitating ASC behavior in cancer and wound healing.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":"31 19-20","pages":"579-592"},"PeriodicalIF":4.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9836707/pdf/scd.2021.0280.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10543346","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}

{"title":"Breast Cancer-Stromal Interactions: Adipose-Derived Stromal/Stem Cell Age and Cancer Subtype Mediated Remodeling.","authors":"Katie M Hamel, Connor T King, Maryn B Cavalier, Kara Q Liimatta, Grace L Rozanski, Timothy A King, Meggie Lam, Grace C Bingham, C Ethan Byrne, Diensn Xing, Bridgette M Collins-Burow, Matthew E Burow, Jorge A Belgodere, Melyssa R Bratton, Bruce A Bunnell, Elizabeth C Martin","doi":"10.1089/scd.2021.0279","DOIUrl":"10.1089/scd.2021.0279","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Adipose tissue is characterized as an endocrine organ that acts as a source of hormones and paracrine factors. In diseases such as cancer, endocrine and paracrine signals from adipose tissue contribute to cancer progression. Young individuals with estrogen receptor-alpha positive (ER-α&lt;sup&gt;+&lt;/sup&gt;) breast cancer (BC) have an increased resistance to endocrine therapies, suggesting that alternative estrogen signaling is activated within these cells. Despite this, the effects of stromal age on the endocrine response in BC are not well defined. To identify differences between young and aged ER-α&lt;sup&gt;+&lt;/sup&gt; breast tumors, RNA sequencing data were obtained from The Cancer Genome Atlas. Analysis revealed enrichment of matrix and paracrine factors in young (≤40 years old) patients compared to aged (≥65 years old) tumor samples. Adipose-derived stromal/stem cells (ASCs) from noncancerous lipoaspirate of young and aged donors were evaluated for alterations in matrix production and paracrine secreted factors to determine if the tumor stroma could alter estrogen signaling. Young and aged ASCs demonstrated comparable proliferation, differentiation, and matrix production, but exhibited differences in the expression levels of inflammatory cytokines (Interferon gamma, interleukin [IL]-8, IL-10, Tumor necrosis factor alpha, IL-2, and IL-6). Conditioned media (CM)-based experiments showed that young ASC donor age elevated endocrine response in ER-α&lt;sup&gt;+&lt;/sup&gt; BC cell lines. MCF-7 ER-α&lt;sup&gt;+&lt;/sup&gt; BC cell line treated with secreted factors from young ASCs had enhanced ER-α regulated genes (PGR and SDF-1) compared to MCF-7 cells treated with aged ASC CM. Western blot analysis demonstrated increased activation levels of p-ER ser-167 in the MCF-7 cell line treated with young ASC secreted factors. To determine if ER-α&lt;sup&gt;+&lt;/sup&gt; BC cells heightened the cytokine release in ASCs, ASCs were stimulated with MCF-7-derived CM. Results demonstrated no change in growth factors or cytokines when treated with the ER-α&lt;sup&gt;+&lt;/sup&gt; secretome. In contrast to ER-α&lt;sup&gt;+&lt;/sup&gt; CM, the ER-α negative MDA-MB-231 derived CM demonstrated increased stimulation of pro-inflammatory cytokines in ASCs. While there was no observed change in the release of selected paracrine factors, MCF-7 cells did induce matrix production and a pro-adipogenic lineage commitment. The adipogenesis was evident by increased collagen content through Sirius Red/Fast Green Collagen stain, lipid accumulation evident by Oil Red O stain, and significantly increased expression in PPARγ mRNA expression. The data from this study provide evidence suggesting more of a subtype-dependent than an age-dependent difference in stromal response to BC, suggesting that this signaling is not heightened by reciprocal signals from ER-α&lt;sup&gt;+&lt;/sup&gt; BC cell lines. These results are important in understanding the mechanisms of estrogen signaling and the dynamic and reciprocal nature of cancer cell-stromal cell crosstalk that can l","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":"31 19-20","pages":"604-620"},"PeriodicalIF":4.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9595652/pdf/scd.2021.0279.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9707989","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}

{"title":"Uncoupling of Proliferative Capacity from Developmental Stage During Directed Cardiac Differentiation of Pluripotent Stem Cells.","authors":"Katherine Minter-Dykhouse,&nbsp;Timothy J Nelson,&nbsp;Clifford D L Folmes","doi":"10.1089/scd.2022.0041","DOIUrl":"https://doi.org/10.1089/scd.2022.0041","url":null,"abstract":"<p><p>Lineage-specific differentiation of human-induced pluripotent stem cells (hiPSCs) into cardiomyocytes (CMs) offers a patient-specific model to dissect development and disease pathogenesis in a dish. However, challenges exist with this model system, such as the relative immaturity of iPSC-derived CMs, which evoke the question of whether this model faithfully recapitulates in vivo cardiac development. As in vivo cardiac developmental stage is intimately linked with the proliferative capacity (or maturation is inversely correlated to proliferative capacity), we sought to understand how proliferation is regulated during hiPSC CM differentiation and how it compares with in vivo mouse cardiac development. Using standard Chemically Defined Media 3 differentiation, gene expression profiles demonstrate that hiPSC-derived cardiomyocytes (hiPSC-CMs) do not progress past the equivalent of embryonic day 14.5 of murine cardiac development. Throughout differentiation, overall DNA synthesis rapidly declines with <5% of hiPSC-CMs actively synthesizing DNA at the end of the differentiation period despite their immaturity. Bivariate cell cycle analysis demonstrated that hiPSC-CMs have a cell cycle profile distinct from their non-cardiac counterparts from the same differentiation, with significantly fewer cells within G1 and a marked accumulation of cells in G2/M than their non-cardiac counterparts throughout differentiation. Pulse-chase analysis demonstrated that non-cardiac cells progressed completely through the cell cycle within a 24-h period, whereas hiPSC-CMs had restricted progression with only a small proportion of cells undergoing cytokinesis with the remainder stalling in late S-phase or G2/M. This cell cycle arrest phenotype is associated with abbreviated expression of cell cycle promoting genes compared with expression throughout murine embryonic cardiac development. In summary, directed differentiation of hiPSCs into CMs uncouples the developmental stage from cell cycle regulation compared with in vivo mouse cardiac development, leading to a premature exit of hiPSC-CMs from the cell cycle despite their relative immaturity.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":"31 17-18","pages":"521-528"},"PeriodicalIF":4.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9641990/pdf/scd.2022.0041.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10129797","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}

{"title":"A Molecular Analysis of Neural Olfactory Placode Differentiation in Human Pluripotent Stem Cells.","authors":"Rebecca L Bricker,&nbsp;Uchit Bhaskar,&nbsp;Rossella Titone,&nbsp;Melanie A Carless,&nbsp;Tiziano Barberi","doi":"10.1089/scd.2021.0257","DOIUrl":"https://doi.org/10.1089/scd.2021.0257","url":null,"abstract":"<p><p>During embryonic development, the olfactory sensory neurons (OSNs) and the gonadotropic-releasing hormone neurons (GNRHNs) migrate from the early nasal cavity, known as the olfactory placode, to the brain. Defects in the development of OSNs and GNRHNs result in neurodevelopmental disorders such as anosmia and congenital hypogonadotropic hypogonadism, respectively. Treatments do not restore the defective neurons in these disorders, and as a result, patients have a diminished sense of smell or a gonadotropin hormone deficiency. Human pluripotent stem cells (hPSCs) can produce any cell type in the body; therefore, they are an invaluable tool for cell replacement therapies. Transplantation of olfactory placode progenitors, derived from hPSCs, is a promising therapeutic to replace OSNs and GNRHNs and restore tissue function. Protocols to generate olfactory placode progenitors are limited, and thus, we describe, in this study, a novel in vitro model for olfactory placode differentiation in hPSCs, which is capable of producing both OSNs and GNRHNs. Our study investigates the major developmental signaling factors that recapitulate the embryonic development of the olfactory tissue. We demonstrate that induction of olfactory placode in hPSCs requires bone morphogenetic protein inhibition, wingless/integrated protein inhibition, retinoic acid inhibition, transforming growth factor alpha activation, and fibroblast growth factor 8 activation. We further show that the protocol transitions hPSCs through the anterior pan-placode ectoderm and neural ectoderm regions in early development while preventing neural crest and non-neural ectoderm regions. Finally, we demonstrate production of OSNs and GNRHNs by day 30 of differentiation. Our study is the first to report on OSN differentiation in hPSCs.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":"31 17-18","pages":"507-520"},"PeriodicalIF":4.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9641992/pdf/scd.2021.0257.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10129288","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}