{"title":"Screening of factors inducing alveolar type 1 epithelial cells using human pluripotent stem cells.","authors":"Yuko Ohnishi, Atsushi Masui, Takahiro Suezawa, Ryuta Mikawa, Toyohiro Hirai, Masatoshi Hagiwara, Shimpei Gotoh","doi":"10.1016/j.stemcr.2024.02.009","DOIUrl":"10.1016/j.stemcr.2024.02.009","url":null,"abstract":"<p><p>Alveolar type 2 (AT2) epithelial cells are tissue stem cells capable of differentiating into alveolar type 1 (AT1) cells for injury repair and maintenance of lung homeostasis. However, the factors involved in human AT2-to-AT1 cell differentiation are not fully understood. Here, we established SFTPC<sup>GFP</sup> and AGER<sup>mCherry-HiBiT</sup> dual-reporter induced pluripotent stem cells (iPSCs), which detected AT2-to-AT1 cell differentiation with high sensitivity and identified factors inducing AT1 cell differentiation from AT2 and their progenitor cells. We also established an \"on-gel\" alveolar epithelial spheroid culture suitable for medium-throughput screening. Among the 274 chemical compounds, several single compounds, including LATS-IN-1, converted AT1 cells from AT2 and their progenitor cells. Moreover, YAP/TAZ signaling activation and AKT signaling suppression synergistically recapitulated the induction of transcriptomic, morphological, and functionally mature AT1 cells. Our findings provide novel insights into human lung development and lung regenerative medicine.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"529-544"},"PeriodicalIF":5.9,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11096435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140327183","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 : 2024-04-09Epub Date: 2024-03-28DOI: 10.1016/j.stemcr.2024.02.008
Megan Obi, Ashley Adams, Alexandria Vandenbossche, Ana Otero Pineiro, Amy L Lightner
{"title":"Patient engagement and satisfaction with early phase cell therapy clinical trials at a tertiary inflammatory bowel disease center.","authors":"Megan Obi, Ashley Adams, Alexandria Vandenbossche, Ana Otero Pineiro, Amy L Lightner","doi":"10.1016/j.stemcr.2024.02.008","DOIUrl":"10.1016/j.stemcr.2024.02.008","url":null,"abstract":"<p><p>Several clinical trials are underway investigating cell and gene therapy, and while these trials are meant to significantly impact patient care, they rely on patient engagement and participation. Unfortunately, clinical trials generally require extensive commitment by subjects. While several studies are using validated surveys to measure patient-reported outcomes, there is a lack of characterization of the patient experience as a subject in these trials. As such, we surveyed mesenchymal stromal cell (MSC) trial participants to understand their perspective. We found that there exists a reliance on one's gastroenterologist and colorectal surgeons for trial introduction and that time and cost were the main barriers to participation. Overall, participants demonstrated high satisfaction with MSC trial participation, but future protocols could incorporate increased use of virtual appointments to optimize patient experience.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"435-442"},"PeriodicalIF":5.9,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11096429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140327181","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 : 2024-04-09Epub Date: 2024-03-28DOI: 10.1016/j.stemcr.2024.02.012
Chaahat S B Singh, Kelly Marie Johns, Suresh Kari, Lonna Munro, Angela Mathews, Franz Fenninger, Cheryl G Pfeifer, Wilfred A Jefferies
{"title":"Conclusive demonstration of iatrogenic Alzheimer's disease transmission in a model of stem cell transplantation.","authors":"Chaahat S B Singh, Kelly Marie Johns, Suresh Kari, Lonna Munro, Angela Mathews, Franz Fenninger, Cheryl G Pfeifer, Wilfred A Jefferies","doi":"10.1016/j.stemcr.2024.02.012","DOIUrl":"10.1016/j.stemcr.2024.02.012","url":null,"abstract":"<p><p>The risk of iatrogenic disease is often underestimated as a concern in contemporary medical procedures, encompassing tissue and organ transplantation, stem cell therapies, blood transfusions, and the administration of blood-derived products. In this context, despite the prevailing belief that Alzheimer's disease (AD) manifests primarily in familial and sporadic forms, our investigation reveals an unexpected transplantable variant of AD in a preclinical context, potentially indicating iatrogenic transmission in AD patients. Through adoptive transplantation of donor bone marrow stem cells carrying a mutant human amyloid precursor protein (APP) transgene into either APP-deficient knockout or normal recipient animals, we observed rapid development of AD pathological hallmarks. These pathological features were significantly accelerated and emerged within 6-9 months post transplantation and included compromised blood-brain barrier integrity, heightened cerebral vascular neoangiogenesis, elevated brain-associated β-amyloid levels, and cognitive impairment. Furthermore, our findings underscore the contribution of β-amyloid burden originating outside of the central nervous system to AD pathogenesis within the brain. We conclude that stem cell transplantation from donors harboring a pathogenic mutant allele can effectively transfer central nervous system diseases to healthy recipients, mirroring the pathogenesis observed in the donor. Consequently, our observations advocate for genomic sequencing of donor specimens prior to tissue, organ, or stem cell transplantation therapies, as well as blood transfusions and blood-derived product administration, to mitigate the risk of iatrogenic diseases.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"456-468"},"PeriodicalIF":5.9,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11096610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140327178","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 : 2024-04-09Epub Date: 2024-03-21DOI: 10.1016/j.stemcr.2024.03.006
Hannah A Pizzato, Paula Alonso-Guallart, James Woods, Bjarki Johannesson, Jon P Connelly, Todd A Fehniger, John P Atkinson, Shondra M Pruett-Miller, Frederick J Monsma, Deepta Bhattacharya
{"title":"Engineering human pluripotent stem cell lines to evade xenogeneic transplantation barriers.","authors":"Hannah A Pizzato, Paula Alonso-Guallart, James Woods, Bjarki Johannesson, Jon P Connelly, Todd A Fehniger, John P Atkinson, Shondra M Pruett-Miller, Frederick J Monsma, Deepta Bhattacharya","doi":"10.1016/j.stemcr.2024.03.006","DOIUrl":"10.1016/j.stemcr.2024.03.006","url":null,"abstract":"","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"596"},"PeriodicalIF":5.9,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11096595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140190170","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":"Micro-patterned culture of iPSC-derived alveolar and airway cells distinguishes SARS-CoV-2 variants.","authors":"Atsushi Masui, Rina Hashimoto, Yasufumi Matsumura, Takuya Yamamoto, Miki Nagao, Takeshi Noda, Kazuo Takayama, Shimpei Gotoh","doi":"10.1016/j.stemcr.2024.02.011","DOIUrl":"10.1016/j.stemcr.2024.02.011","url":null,"abstract":"<p><p>The emergence of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) variants necessitated a rapid evaluation system for their pathogenesis. Lung epithelial cells are their entry points; however, in addition to their limited source, the culture of human alveolar epithelial cells is especially complicated. Induced pluripotent stem cells (iPSCs) are an alternative source of human primary stem cells. Here, we report a model for distinguishing SARS-CoV-2 variants at high resolution, using separately induced iPSC-derived alveolar and airway cells in micro-patterned culture plates. The position-specific signals induced the apical-out alveolar type 2 and multiciliated airway cells at the periphery and center of the colonies, respectively. The infection studies in each lineage enabled profiling of the pathogenesis of SARS-CoV-2 variants: infection efficiency, tropism to alveolar and airway lineages, and their responses. These results indicate that this culture system is suitable for predicting the pathogenesis of emergent SARS-CoV-2 variants.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"545-561"},"PeriodicalIF":5.9,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11096626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140327179","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 : 2024-04-09Epub Date: 2024-03-28DOI: 10.1016/j.stemcr.2024.03.001
Yingnan Lei, Diana Al Delbany, Nuša Krivec, Marius Regin, Edouard Couvreu de Deckersberg, Charlotte Janssens, Manjusha Ghosh, Karen Sermon, Claudia Spits
{"title":"SALL3 mediates the loss of neuroectodermal differentiation potential in human embryonic stem cells with chromosome 18q loss.","authors":"Yingnan Lei, Diana Al Delbany, Nuša Krivec, Marius Regin, Edouard Couvreu de Deckersberg, Charlotte Janssens, Manjusha Ghosh, Karen Sermon, Claudia Spits","doi":"10.1016/j.stemcr.2024.03.001","DOIUrl":"10.1016/j.stemcr.2024.03.001","url":null,"abstract":"<p><p>Human pluripotent stem cell (hPSC) cultures are prone to genetic drift, because cells that have acquired specific genetic abnormalities experience a selective advantage in vitro. These abnormalities are highly recurrent in hPSC lines worldwide, but their functional consequences in differentiating cells are scarcely described. In this work, we show that the loss of chromosome 18q impairs neuroectoderm commitment and that downregulation of SALL3, a gene located in the common 18q loss region, is responsible for this failed neuroectodermal differentiation. Knockdown of SALL3 in control lines impaired differentiation in a manner similar to the loss of 18q, and transgenic overexpression of SALL3 in hESCs with 18q loss rescued the differentiation capacity of the cells. Finally, we show that loss of 18q and downregulation of SALL3 leads to changes in the expression of genes involved in pathways regulating pluripotency and differentiation, suggesting that these cells are in an altered state of pluripotency.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"562-578"},"PeriodicalIF":5.9,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11096619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140327182","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 : 2024-04-09Epub Date: 2024-03-07DOI: 10.1016/j.stemcr.2024.02.004
Safa F Mohamad, Roy El Koussa, Joydeep Ghosh, Rachel Blosser, Andrea Gunawan, Justin Layer, Chi Zhang, Sonali Karnik, Utpal Davé, Melissa A Kacena, Edward F Srour
{"title":"Osteomacs promote maintenance of murine hematopoiesis through megakaryocyte-induced upregulation of Embigin and CD166.","authors":"Safa F Mohamad, Roy El Koussa, Joydeep Ghosh, Rachel Blosser, Andrea Gunawan, Justin Layer, Chi Zhang, Sonali Karnik, Utpal Davé, Melissa A Kacena, Edward F Srour","doi":"10.1016/j.stemcr.2024.02.004","DOIUrl":"10.1016/j.stemcr.2024.02.004","url":null,"abstract":"<p><p>Maintenance of hematopoietic stem cell (HSC) function in the niche is an orchestrated event. Osteomacs (OM) are key cellular components of the niche. Previously, we documented that osteoblasts, OM, and megakaryocytes interact to promote hematopoiesis. Here, we further characterize OM and identify megakaryocyte-induced mediators that augment the role of OM in the niche. Single-cell mRNA-seq, mass spectrometry, and CyTOF examination of megakaryocyte-stimulated OM suggested that upregulation of CD166 and Embigin on OM augment their hematopoiesis maintenance function. CD166 knockout OM or shRNA-Embigin knockdown OM confirmed that the loss of these molecules significantly reduced the ability of OM to augment the osteoblast-mediated hematopoietic-enhancing activity. Recombinant CD166 and Embigin partially substituted for OM function, characterizing both proteins as critical mediators of OM hematopoietic function. Our data identify Embigin and CD166 as OM-regulated critical components of HSC function in the niche and potential participants in various in vitro manipulations of stem cells.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"486-500"},"PeriodicalIF":5.9,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11096441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140065983","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 : 2024-04-09Epub Date: 2024-03-21DOI: 10.1016/j.stemcr.2024.02.005
Maria I Bergamasco, Nishika Ranathunga, Waruni Abeysekera, Connie S N Li-Wai-Suen, Alexandra L Garnham, Simon N Willis, Helen M McRae, Yuqing Yang, Angela D'Amico, Ladina Di Rago, Stephen Wilcox, Stephen L Nutt, Warren S Alexander, Gordon K Smyth, Anne K Voss, Tim Thomas
{"title":"The histone acetyltransferase KAT6B is required for hematopoietic stem cell development and function.","authors":"Maria I Bergamasco, Nishika Ranathunga, Waruni Abeysekera, Connie S N Li-Wai-Suen, Alexandra L Garnham, Simon N Willis, Helen M McRae, Yuqing Yang, Angela D'Amico, Ladina Di Rago, Stephen Wilcox, Stephen L Nutt, Warren S Alexander, Gordon K Smyth, Anne K Voss, Tim Thomas","doi":"10.1016/j.stemcr.2024.02.005","DOIUrl":"10.1016/j.stemcr.2024.02.005","url":null,"abstract":"<p><p>The histone lysine acetyltransferase KAT6B (MYST4, MORF, QKF) is the target of recurrent chromosomal translocations causing hematological malignancies with poor prognosis. Using Kat6b germline deletion and overexpression in mice, we determined the role of KAT6B in the hematopoietic system. We found that KAT6B sustained the fetal hematopoietic stem cell pool but did not affect viability or differentiation. KAT6B was essential for normal levels of histone H3 lysine 9 (H3K9) acetylation but not for a previously proposed target, H3K23. Compound heterozygosity of Kat6b and the closely related gene, Kat6a, abolished hematopoietic reconstitution after transplantation. KAT6B and KAT6A cooperatively promoted transcription of genes regulating hematopoiesis, including the Hoxa cluster, Pbx1, Meis1, Gata family, Erg, and Flt3. In conclusion, we identified the hematopoietic processes requiring Kat6b and showed that KAT6B and KAT6A synergistically promoted HSC development, function, and transcription. Our findings are pertinent to current clinical trials testing KAT6A/B inhibitors as cancer therapeutics.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"469-485"},"PeriodicalIF":5.9,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11096436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140190172","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":"MST1/2 regulates fibro/adipogenic progenitor fate decisions in skeletal muscle regeneration.","authors":"Kezhi Wang, Jingjing Yang, Yina An, Jing Wang, Shuyu Tan, Hui Xu, Yanjun Dong","doi":"10.1016/j.stemcr.2024.02.010","DOIUrl":"10.1016/j.stemcr.2024.02.010","url":null,"abstract":"<p><p>Defective skeletal muscle regeneration is often accompanied by fibrosis. Fibroblast/adipose progenitors (FAPs) are important in these processes, however, the regulation of FAP fate decisions is unclear. Here, using inducible conditional knockout mice, we show that blocking mammalian Ste20-like kinases 1/2 (MST1/2) of FAPs prevented apoptosis and reduced interleukin-6 secretion in vivo and in vitro, which impaired myoblast proliferation and differentiation, as well as impaired muscle regeneration. Deletion of Mst1/2 increased co-localization of Yes-associated protein (YAP) with Smad2/3 in nuclei and promoted differentiation of FAPs toward myofibroblasts, resulting in excessive collagen deposition and skeletal muscle fibrosis. Meanwhile, inhibition of MST1/2 increased YAP/Transcriptional co-activator with PDZ-binding motif activation, which promoted activation of the WNT/β-catenin pathway and impaired the differentiation of FAPs toward adipocytes. These results reveal a new mechanism for MST1/2 action in disrupted skeletal muscle regeneration and fibrosis via regulation of FAP apoptosis and differentiation. MST1/2 is a potential therapeutic target for the treatment of some myopathies.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"501-514"},"PeriodicalIF":5.9,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11096422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140327180","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 : 2024-04-01DOI: 10.1016/j.stemcr.2024.03.008
Mindaugas Paužuolis, D. Fatykhova, Boris Zühlke, Torsten Schwecke, Mastura Neyazi, Pilar Samperio-Ventayol, Carmen Aguilar, Nicolas Schlegel, Simon Dökel, Markus Ralser, Andreas Hocke, Christine Krempl, Sina Bartfeld
{"title":"SARS-CoV-2 tropism to intestinal but not gastric epithelial cells is defined by limited ACE2 expression","authors":"Mindaugas Paužuolis, D. Fatykhova, Boris Zühlke, Torsten Schwecke, Mastura Neyazi, Pilar Samperio-Ventayol, Carmen Aguilar, Nicolas Schlegel, Simon Dökel, Markus Ralser, Andreas Hocke, Christine Krempl, Sina Bartfeld","doi":"10.1016/j.stemcr.2024.03.008","DOIUrl":"https://doi.org/10.1016/j.stemcr.2024.03.008","url":null,"abstract":"","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":"401 ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140757637","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}