Stem Cell ReportsPub Date : 2024-12-31DOI: 10.1016/j.stemcr.2024.12.002
Fabrizio Tonelli, Ludovico Iannello, Stefano Gustincich, Angelo Di Garbo, Luca Pandolfini, Federico Cremisi
{"title":"Dual inhibition of MAPK/ERK and BMP signaling induces entorhinal-like identity in mouse ESC-derived pallial progenitors.","authors":"Fabrizio Tonelli, Ludovico Iannello, Stefano Gustincich, Angelo Di Garbo, Luca Pandolfini, Federico Cremisi","doi":"10.1016/j.stemcr.2024.12.002","DOIUrl":"https://doi.org/10.1016/j.stemcr.2024.12.002","url":null,"abstract":"<p><p>The mechanisms that determine distinct embryonic pallial identities remain elusive. The central role of Wnt signaling in directing dorsal telencephalic progenitors to the isocortex or hippocampus has been elucidated. Here, we show that timely inhibition of MAPK/ERK and BMP signaling in neuralized mouse embryonic stem cells (ESCs) specifies a cell identity characteristic of the allocortex. Comparison of the global gene expression profiles of neural cells generated by MAPK/ERK and BMP inhibition (MiBi cells) with those of cells from early postnatal encephalic regions reveals a pallial identity of MiBi cells, distinct from isocortical and hippocampal cells. MiBi cells display a unique pattern of gene expression and connectivity, and share molecular and electrophysiological features with the entorhinal cortex. Our results suggest that early changes in cell signaling can specify distinct pallial fates that are maintained by specific neuronal lineages independent of subsequent embryonic morphogenetic interactions and can determine their functional connectivity.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102387"},"PeriodicalIF":5.9,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stem Cell ReportsPub Date : 2024-12-30DOI: 10.1016/j.stemcr.2024.102391
Rony Chidiac, Andy Yang, Elli Kubarakos, Nicholas Mikolajewicz, Hong Han, Maira P Almeida, Pierre E Thibeault, Sichun Lin, Graham MacLeod, Jean-Philippe Gratton, Jason Moffat, Stephane Angers
{"title":"Selective activation of FZD2 and FZD7 reveals non-redundant function during mesoderm differentiation.","authors":"Rony Chidiac, Andy Yang, Elli Kubarakos, Nicholas Mikolajewicz, Hong Han, Maira P Almeida, Pierre E Thibeault, Sichun Lin, Graham MacLeod, Jean-Philippe Gratton, Jason Moffat, Stephane Angers","doi":"10.1016/j.stemcr.2024.102391","DOIUrl":"https://doi.org/10.1016/j.stemcr.2024.102391","url":null,"abstract":"<p><p>During gastrulation, Wnt-β-catenin signaling dictates lineage bifurcation generating different mesoderm cell types. However, the specific role of Wnt receptors in mesoderm specification remains elusive. Using selective Frizzled (FZD) and LRP5/6 antibody-based agonists, we examined FZD receptors' function during directed mesoderm differentiation of human pluripotent stem cells (hPSCs). We found that FZD2 and FZD7 receptors are expressed at the membrane of hPSCs and that their activation triggers β-catenin signaling with different kinetics, thereby influencing mesoderm patterning choices. Specifically, FZD7 activation enhances both paraxial and lateral mesoderm differentiation, whereas FZD2 activation favors paraxial mesoderm. Mechanistically, FZD2 activation promotes sustained Wnt-β-catenin levels, guiding hPSCs differentiation toward paraxial mesoderm, while blocking lateral mesoderm. In contrast, FZD7 activation kinetics display similar initial activation but more dampening of β-catenin signaling, permitting lateral mesoderm induction in addition to paraxial mesoderm specification. Our findings reveal non-redundant roles for FZD2 and FZD7 in mesoderm specification, offering leverage for precise directed differentiation outcomes.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102391"},"PeriodicalIF":5.9,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143011920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Capture primed pluripotency in guinea pig.","authors":"Jing Guo, Runxia Lin, Jinpeng Liu, Rongrong Liu, Shuyan Chen, Zhen Zhang, Yongzheng Yang, Haiyun Wang, Luqin Wang, Shengyong Yu, Chunhua Zhou, Lizhan Xiao, Rongping Luo, Jinjin Yu, Lihua Zeng, Xiaoli Zhang, Yusha Li, Haokaifeng Wu, Tao Wang, Yi Li, Manish Kumar, Ping Zhu, Jing Liu","doi":"10.1016/j.stemcr.2024.102388","DOIUrl":"https://doi.org/10.1016/j.stemcr.2024.102388","url":null,"abstract":"<p><p>Guinea pigs are valuable models for human disease research, yet the lack of established pluripotent stem cell lines has limited their utility. In this study, we isolate and characterize guinea pig epiblast stem cells (gpEpiSCs) from post-implantation embryos. These cells differentiate into the three germ layers, maintain normal karyotypes, and rely on FGF2 and ACTIVIN A signaling for self-renewal and pluripotency. Wingless/Integrated (WNT) signaling inhibition is also essential for their maintenance. GpEpiSCs express key pluripotency markers (OCT4, SOX2, NANOG) and share transcriptional similarities with human and mouse primed stem cells. While many genes are conserved between guinea pig and human primed stem cells, transcriptional analysis also reveals species-specific differences in pluripotency-related pathways. Epigenetic analysis highlights bivalent gene regulation, underscoring their developmental potential. This work demonstrates both the evolutionary conservation and divergence of primed pluripotent stem cells, providing a new tool for biomedical research and enhancing guinea pigs' utility in studying human diseases.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102388"},"PeriodicalIF":5.9,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stem Cell ReportsPub Date : 2024-12-25DOI: 10.1016/j.stemcr.2024.12.001
Matthew R Arkenberg, Mahboubeh Jafarkhani, Chien-Chi Lin, Eri Hashino
{"title":"Chemically defined and dynamic click hydrogels support hair cell differentiation in human inner ear organoids.","authors":"Matthew R Arkenberg, Mahboubeh Jafarkhani, Chien-Chi Lin, Eri Hashino","doi":"10.1016/j.stemcr.2024.12.001","DOIUrl":"https://doi.org/10.1016/j.stemcr.2024.12.001","url":null,"abstract":"<p><p>The mechanical properties in the inner ear microenvironment play a key role in its patterning during embryonic development. To recapitulate inner ear development in vitro, three-dimensional tissue engineering strategies including the application of representative tissue models and scaffolds are of increasing interest. Human inner ear organoids are a promising model to recapitulate developmental processes; however, the current protocol requires Matrigel that contains ill-defined extracellular matrix components. Here, we implement an alternative, chemically defined, dynamic hydrogel to support the differentiation of human inner ear organoids. Specifically, thiol-norbornene and hydrazide-aldehyde click chemistries are used to fabricate inner ear organoid-laden, gelatin-based scaffolds. We identify optimal formulations to support hair cell development with comparable efficiency and fidelity to Matrigel-cultured organoids. These results suggest that the chemically defined hydrogel may serve as a viable alternative to Matrigel for inner ear tissue engineering.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102386"},"PeriodicalIF":5.9,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Deep-supercooling preservation of stem cell spheroids for chondral defect repairment.","authors":"Jinbin Qiu, Bangrui Yu, Cheng Ren, Tian Wang, Guangjian Zhang, Zhe Jian, Jian Ding, Feng Xu, Haishui Huang","doi":"10.1016/j.stemcr.2024.10.008","DOIUrl":"10.1016/j.stemcr.2024.10.008","url":null,"abstract":"<p><p>Versatile mesenchymal stem cells (MSCs) play an important role in tissue engineering and regenerative medicine. MSCs in 3D spheroid have shown higher secretion and differentiation functions than suspended counterparts, and, thus, in vitro cryopreservation of MSC spheroids is an indispensable technology to bridge the spatiotemporal gaps between spheroid generation and application. Traditional cryopreservation methods are inapplicable for spheroid due to severe thermal stress, toxic cryoprotectants, and ice formation. Here, we constructed and preserved human MSC (hMSC) spheroids via deep supercooling (DSC). Spheroids were DSC preserved at -12°C without ice formation for 7 days, with higher cell viability, energy level, and chondrogenic differentiation capacity than suspended hMSCs. hMSCs embedded in spheroids have close cell-cell interactions via N-cadherin to activate the AKT-cytochrome c-caspase anti-apoptotic cascade during DSC preservation. Finally, preserved hMSC spheroids were capable of chondrogenic differentiation and can be co-delivered with collagen to treat rat cartilage defects in vivo.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1665-1676"},"PeriodicalIF":5.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stem Cell ReportsPub Date : 2024-12-10Epub Date: 2024-11-07DOI: 10.1016/j.stemcr.2024.09.004
Daniela Flores-Gomez, Willemijn Hobo, Diede van Ens, Elise L Kessler, Boris Novakovic, Nicolaas P M Schaap, Wim H C Rijnen, Leo A B Joosten, Mihai G Netea, Niels P Riksen, Siroon Bekkering
{"title":"Interleukin-1β induces trained innate immunity in human hematopoietic progenitor cells in vitro.","authors":"Daniela Flores-Gomez, Willemijn Hobo, Diede van Ens, Elise L Kessler, Boris Novakovic, Nicolaas P M Schaap, Wim H C Rijnen, Leo A B Joosten, Mihai G Netea, Niels P Riksen, Siroon Bekkering","doi":"10.1016/j.stemcr.2024.09.004","DOIUrl":"10.1016/j.stemcr.2024.09.004","url":null,"abstract":"<p><p>Innate immune cells can develop a long-lasting hyperresponsive phenotype, termed trained immunity, mediated by epigenetic and metabolic reprogramming. In mice, exposure to Bacille Calmette-Guérin (BCG), β-glucan, or Western diet induces trained immunity by reprogramming hematopoietic progenitor cells (HPCs), through interleukin-1β (IL-1β) signaling in the bone marrow (BM). We investigated whether IL-1β induces trained immunity in primary human BM-derived HPCs in vitro. We exposed human BM-derived HPCs to IL-1β for 4 h. HPCs were expanded and differentiated into monocytes followed by functional and transcriptomic characterization. IL-1β-exposed HPCs showed higher granulocyte-macrophage colony-forming units. The monocyte offspring produced more tumor necrosis factor (TNF) and IL-1β after restimulation with lipopolysaccharide (LPS) and Pam3Cys and is metabolically more active. Transcriptomic analysis showed upregulation of key atherogenic and inflammatory pathways. In conclusion, brief exposure of human BM-derived HPCs to IL-1β in vitro induces a trained immunity phenotype.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1651-1664"},"PeriodicalIF":5.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stem Cell ReportsPub Date : 2024-12-10Epub Date: 2024-11-07DOI: 10.1016/j.stemcr.2024.10.004
Hendrik J Undeutsch, Alberto Posabella, Andrea B Alber, Pushpinder S Bawa, Carlos Villacorta-Martin, Feiya Wang, Laertis Ikonomou, Darrell N Kotton, Anthony N Hollenberg
{"title":"Derivation of transplantable human thyroid follicular epithelial cells from induced pluripotent stem cells.","authors":"Hendrik J Undeutsch, Alberto Posabella, Andrea B Alber, Pushpinder S Bawa, Carlos Villacorta-Martin, Feiya Wang, Laertis Ikonomou, Darrell N Kotton, Anthony N Hollenberg","doi":"10.1016/j.stemcr.2024.10.004","DOIUrl":"10.1016/j.stemcr.2024.10.004","url":null,"abstract":"<p><p>The production of mature functioning thyroid follicular cells (TFCs) from human induced pluripotent stem cells (iPSCs) is critical for potential novel therapeutic approaches to post-surgical and congenital hypothyroidism. To accomplish this, we developed a novel human iPSC line that expresses fluorophores targeted to the NKX2-1 and PAX8 loci, allowing for the identification and purification of cells destined to become TFCs. Optimizing a sequence of defined, serum-free media to promote stepwise developmental directed differentiation, we found that bone morphogenic protein 4 (BMP4) and fibroblast growth factor 2 (FGF2) stimulated lineage specification into TFCs from multiple iPSC lines. Single-cell RNA sequencing demonstrated that BMP4 withdrawal after lineage specification promoted TFC maturation, with mature TFCs representing the majority of cells present within 1 month. After xenotransplantation into athyreotic immunodeficient mice, engrafted cells exhibited thyroid follicular organization with thyroglobulin protein detected in the lumens of NKX2-1-positive follicles. While our iPSC-derived TFCs presented durable expression of thyroid-specific proteins, they were unable to rescue hypothyroidism in vivo.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1690-1705"},"PeriodicalIF":5.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Bone morphogenetic protein 4 induces hematopoietic stem cell development from murine hemogenic endothelial cells in culture.","authors":"Mariko Tsuruda, Saori Morino-Koga, Xueyu Zhao, Shingo Usuki, Kei-Ichiro Yasunaga, Tomomasa Yokomizo, Ryuichi Nishinakamura, Toshio Suda, Minetaro Ogawa","doi":"10.1016/j.stemcr.2024.10.005","DOIUrl":"10.1016/j.stemcr.2024.10.005","url":null,"abstract":"<p><p>Hematopoietic stem cells (HSCs) develop from hemogenic endothelial cells (HECs) during mouse embryogenesis. Understanding the signaling molecules required for HSC development is crucial for the in vitro derivation of HSCs. We previously induced HSCs from embryonic HECs, isolated at embryonic day 10.5 (E10.5), in serum-free culture conditions with stem cell factor, thrombopoietin, and an endothelial feeder layer. Here, we aimed to elucidate signal requirements for inducing HSCs from earlier-stage HECs. Single-cell RNA sequencing (RNA-seq) analysis detected bone morphogenetic protein (BMP) signaling activation in E9.5 HECs. Adding BMP4 to the culture conditions led to the induction of HSCs from E9.5 HECs. Furthermore, isolating BMP4 receptor-expressing HECs from E9.5 embryos enriched progenitors with HSC-forming ability. This study identified BMP4 as an essential factor promoting the differentiation of early HECs into HSCs, opening up new possibilities for the in vitro derivation of HSCs.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1677-1689"},"PeriodicalIF":5.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stem Cell ReportsPub Date : 2024-12-10Epub Date: 2024-11-14DOI: 10.1016/j.stemcr.2024.10.006
Tsunakuni Ikka, Taichi Hatta, Misao Fujita
{"title":"Amendments to ASRM: Can we move away from a \"Therapeutic Haven\"?","authors":"Tsunakuni Ikka, Taichi Hatta, Misao Fujita","doi":"10.1016/j.stemcr.2024.10.006","DOIUrl":"10.1016/j.stemcr.2024.10.006","url":null,"abstract":"<p><p>The key amendment to the Act on the Safety of Regenerative Medicine in June 2024 is regarding on-site inspections and the criteria for disqualifying the Certified Special Committees for Regenerative Medicine and Certified Committees for Regenerative Medicine. Appropriate regulations are needed after the legal amendment to stop the widespread use of unproven interventions and move away from the concept of a \"Therapeutic Haven.\"</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1648-1650"},"PeriodicalIF":5.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stem Cell ReportsPub Date : 2024-12-10Epub Date: 2024-11-27DOI: 10.1016/j.stemcr.2024.10.007
Anna C Seubert, Marion Krafft, Sarah Bopp, Moutaz Helal, Pranjali Bhandare, Elmar Wolf, Anna Alemany, Angela Riedel, Kai Kretzschmar
{"title":"Spatial transcriptomics reveals molecular cues underlying the site specificity of the adult mouse oral mucosa and its stem cell niches.","authors":"Anna C Seubert, Marion Krafft, Sarah Bopp, Moutaz Helal, Pranjali Bhandare, Elmar Wolf, Anna Alemany, Angela Riedel, Kai Kretzschmar","doi":"10.1016/j.stemcr.2024.10.007","DOIUrl":"10.1016/j.stemcr.2024.10.007","url":null,"abstract":"<p><p>The oral cavity is a multifunctional organ composed of structurally heterogeneous mucosal tissues that remain poorly characterized. Oral mucosal tissues are highly stratified and segmented along an epithelial-lamina propria axis. Here, we performed spatial transcriptomics (tomo-seq) on the tongue, cheeks, and palate of the adult mouse to understand the cues that maintain the oral mucosal sites. We define molecular markers of unique and shared cellular niches and differentiation programs across oral sites. Using a comparative approach, we identify fibroblast growth factor (FGF) pathway components as potential stem cell niche factors for oral epithelial stem cells. Using organoid-forming efficiency assays, we validated three FGF ligands (FGF1, FGF7, and FGF10) as site-specific niche factors in the dorsal and ventral tongue. Our dataset of the spatially resolved genes across major oral sites represents a comprehensive resource for unraveling the molecular mechanisms underlying the adult homeostasis of the oral mucosa and its stem cell niches.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1706-1719"},"PeriodicalIF":5.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}