Stem Cell Reports最新文献

Nascent matrix deposition supports alveolar organoid formation from aggregates in synthetic hydrogels.

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-12-12 DOI: 10.1016/j.stemcr.2024.11.006

Madeline K Eiken, Charlie J Childs, Lindy K Brastrom, Tristan Frum, Eleanor M Plaster, Donia W Ahmed, Ryan C Spencer, Orren Shachaf, Suzanne Pfeiffer, Justin E Levine, Konstantinos-Dionysios Alysandratos, Darrell N Kotton, Jason R Spence, Claudia Loebel

{"title":"Nascent matrix deposition supports alveolar organoid formation from aggregates in synthetic hydrogels.","authors":"Madeline K Eiken, Charlie J Childs, Lindy K Brastrom, Tristan Frum, Eleanor M Plaster, Donia W Ahmed, Ryan C Spencer, Orren Shachaf, Suzanne Pfeiffer, Justin E Levine, Konstantinos-Dionysios Alysandratos, Darrell N Kotton, Jason R Spence, Claudia Loebel","doi":"10.1016/j.stemcr.2024.11.006","DOIUrl":"10.1016/j.stemcr.2024.11.006","url":null,"abstract":"Human induced pluripotent stem cell (iPSC)-derived alveolar organoids have emerged as a system to model the alveolar epithelium in homeostasis and disease. However, alveolar organoids are typically grown in Matrigel, a mouse sarcoma-derived basement membrane matrix that offers poor control over matrix properties, prompting the development of synthetic hydrogels as a Matrigel alternative. Here, we develop a two-step culture method that involves pre-aggregation of organoids in hydrogel-based microwells followed by embedding in a synthetic hydrogel that supports alveolar organoid growth, while also offering considerable control over organoid and hydrogel properties. We find that the aggregated organoids secrete their own nascent extracellular matrix (ECM) both in the microwells and upon embedding in synthetic hydrogels, which supports their growth. Thus, the synthetic hydrogels described here allow us to de-couple exogenous and nascent ECM to interrogate the role of ECM in organoid formation.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102376"},"PeriodicalIF":5.9,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822704","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}

引用次数: 0

Elevated hematopoietic stem cell frequency in mouse alveolar bone marrow.

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-12-11 DOI: 10.1016/j.stemcr.2024.11.004

Kouta Niizuma, Satoru Morikawa, Eric Gars, Jinyi Xiang, Tomoko Matsubara-Takahashi, Rei Saito, Eri Takematsu, Yuting Wang, Haojun Xu, Arata Wakimoto, Tze Kai Tan, Yoshiaki Kubota, Charles K F Chan, Irving L Weissman, Taneaki Nakagawa, Adam C Wilkinson, Hiromitsu Nakauchi, Ryo Yamamoto

{"title":"Elevated hematopoietic stem cell frequency in mouse alveolar bone marrow.","authors":"Kouta Niizuma, Satoru Morikawa, Eric Gars, Jinyi Xiang, Tomoko Matsubara-Takahashi, Rei Saito, Eri Takematsu, Yuting Wang, Haojun Xu, Arata Wakimoto, Tze Kai Tan, Yoshiaki Kubota, Charles K F Chan, Irving L Weissman, Taneaki Nakagawa, Adam C Wilkinson, Hiromitsu Nakauchi, Ryo Yamamoto","doi":"10.1016/j.stemcr.2024.11.004","DOIUrl":"https://doi.org/10.1016/j.stemcr.2024.11.004","url":null,"abstract":"Hematopoietic stem cells (HSCs) are crucial for maintaining hematopoietic homeostasis and are localized within distinct bone marrow (BM) niches. While BM niches are often considered similar across different skeletal sites, we discovered that the alveolar BM (al-BM) in the mandible harbors the highest frequency of immunophenotypic HSCs in nine different skeletal sites. Transplantation assays revealed significantly increased engraftment from al-BM compared to femur, tibia, or pelvis BM, likely due to a higher proportion of alveolar HSCs. Moreover, hematopoietic progenitor cells (c-Kit+ Sca-1+ Lin-) in al-BM exhibited increased quiescence and reduced apoptosis, indicating superior maintenance and survival characteristics. We also observed an enrichment of mesenchymal stromal cells and skeletal stem cells in al-BM, suggesting a more supportive microenvironment. These findings indicate that al-BM provides a unique microenvironment conducive to higher frequency of HSCs, offering new insights into site-specific hematopoiesis.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102374"},"PeriodicalIF":5.9,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822703","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}

引用次数: 0

Deep-supercooling preservation of stem cell spheroids for chondral defect repairment. 用于软骨缺损修复的干细胞球体的深度过冷保存。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-12-10 Epub Date: 2024-11-21 DOI: 10.1016/j.stemcr.2024.10.008

Jinbin Qiu, Bangrui Yu, Cheng Ren, Tian Wang, Guangjian Zhang, Zhe Jian, Jian Ding, Feng Xu, Haishui Huang

{"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":"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.","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":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Interleukin-1β induces trained innate immunity in human hematopoietic progenitor cells in vitro. 白细胞介素-1β可诱导体外人类造血祖细胞产生训练有素的先天性免疫。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-12-10 Epub Date: 2024-11-07 DOI: 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":"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.","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":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Derivation of transplantable human thyroid follicular epithelial cells from induced pluripotent stem cells. 从诱导多能干细胞中衍生出可移植的人类甲状腺滤泡上皮细胞。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-12-10 Epub Date: 2024-11-07 DOI: 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":"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.","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":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bone morphogenetic protein 4 induces hematopoietic stem cell development from murine hemogenic endothelial cells in culture. 骨形态发生蛋白 4 可诱导小鼠造血内皮细胞的造血干细胞发育。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-12-10 Epub Date: 2024-11-14 DOI: 10.1016/j.stemcr.2024.10.005

Mariko Tsuruda, Saori Morino-Koga, Xueyu Zhao, Shingo Usuki, Kei-Ichiro Yasunaga, Tomomasa Yokomizo, Ryuichi Nishinakamura, Toshio Suda, Minetaro Ogawa

{"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":"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.","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":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Amendments to ASRM: Can we move away from a "Therapeutic Haven"? ASRM 修正案：我们能否放弃 "治疗天堂"？

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-12-10 Epub Date: 2024-11-14 DOI: 10.1016/j.stemcr.2024.10.006

Tsunakuni Ikka, Taichi Hatta, Misao Fujita

引用次数: 0

Spatial transcriptomics reveals molecular cues underlying the site specificity of the adult mouse oral mucosa and its stem cell niches. 空间转录组学揭示了成年小鼠口腔黏膜及其干细胞龛位部位特异性的分子线索。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-12-10 Epub Date: 2024-11-27 DOI: 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":"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.","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":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Message from the editor-in-chief.

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-12-10 DOI: 10.1016/j.stemcr.2024.11.005

Martin F Pera

引用次数: 0

Glycogen synthase kinase-3 inhibition and insulin enhance proliferation and inhibit maturation of human iPSC-derived cardiomyocytes via TCF and FOXO signaling.

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-12-05 DOI: 10.1016/j.stemcr.2024.11.001

Qianliang Yuan, Devin Verbueken, Rafeeh Dinani, Rosa Kim, Eric Schoger, Chloé D Morsink, Shamim Amiri Simkooei, Luuk J M Kemna, Jesper Hjortnaes, Diederik W D Kuster, Reinier A Boon, Laura Cecilia Zelarayan, Jolanda van der Velden, Jan W Buikema

{"title":"Glycogen synthase kinase-3 inhibition and insulin enhance proliferation and inhibit maturation of human iPSC-derived cardiomyocytes via TCF and FOXO signaling.","authors":"Qianliang Yuan, Devin Verbueken, Rafeeh Dinani, Rosa Kim, Eric Schoger, Chloé D Morsink, Shamim Amiri Simkooei, Luuk J M Kemna, Jesper Hjortnaes, Diederik W D Kuster, Reinier A Boon, Laura Cecilia Zelarayan, Jolanda van der Velden, Jan W Buikema","doi":"10.1016/j.stemcr.2024.11.001","DOIUrl":"10.1016/j.stemcr.2024.11.001","url":null,"abstract":"Embryonic signaling pathways exert stage-specific effects during cardiac development, yet the precise signals for proliferation or maturation remain elusive. To uncover the cues for proliferation, we performed a combinatory cell-cycle screen for insulin and glycogen synthase kinase-3 (GSK3) inhibition in spontaneously beating human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Our analysis for proliferation, and subsequential downstream sarcomere development, gene expression analysis, and molecular interventions identified a temporal interplay between insulin/Akt/FOXO and CHIR99021/Wnt/GSK3/TCF signaling. Combined pathway activation led to proliferation of immature hiPSC-CMs with low sarcomere and mitochondria content, while, in the absence of pathway activators, cardiomyocytes rapidly exited the cell cycle and fetched higher organization of sarcomeres and mitochondria. Our data demonstrate two important pathways, which enhance proliferation and inhibit maturation, and provide molecular mechanistic understanding of these cell fate decisions in immature hiPSC-CMs.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102371"},"PeriodicalIF":5.9,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792173","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}

引用次数: 0