Stem Cell Reports最新文献_第7页

Disruption of common ocular developmental pathways in patient-derived optic vesicle models of microphthalmia. 小眼症患者视囊模型中常见的眼部发育途径受到破坏。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-06-11 Epub Date: 2024-05-30 DOI: 10.1016/j.stemcr.2024.05.001

Jonathan Eintracht, Nicholas Owen, Philippa Harding, Mariya Moosajee

{"title":"Disruption of common ocular developmental pathways in patient-derived optic vesicle models of microphthalmia.","authors":"Jonathan Eintracht, Nicholas Owen, Philippa Harding, Mariya Moosajee","doi":"10.1016/j.stemcr.2024.05.001","DOIUrl":"10.1016/j.stemcr.2024.05.001","url":null,"abstract":"Genetic perturbations influencing early eye development can result in microphthalmia, anophthalmia, and coloboma (MAC). Over 100 genes are associated with MAC, but little is known about common disease mechanisms. In this study, we generated induced pluripotent stem cell (iPSC)-derived optic vesicles (OVs) from two unrelated microphthalmia patients and healthy controls. At day 20, 35, and 50, microphthalmia patient OV diameters were significantly smaller, recapitulating the \"small eye\" phenotype. RNA sequencing (RNA-seq) analysis revealed upregulation of apoptosis-initiating and extracellular matrix (ECM) genes at day 20 and 35. Western blot and immunohistochemistry revealed increased expression of lumican, nidogen, and collagen type IV, suggesting ECM overproduction. Increased apoptosis was observed in microphthalmia OVs with reduced phospho-histone 3 (pH3+) cells confirming decreased cell proliferation at day 35. Pharmacological inhibition of caspase-8 activity with Z-IETD-FMK decreased apoptosis in one patient model, highlighting a potential therapeutic approach. These data reveal shared pathophysiological mechanisms contributing to a microphthalmia phenotype.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11390689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141184634","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}

引用次数: 0

Functional mouse hepatocytes derived from interspecies chimeric livers effectively mitigate chronic liver fibrosis. 源自种间嵌合肝脏的功能性小鼠肝细胞可有效缓解慢性肝纤维化。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-06-11 Epub Date: 2024-05-09 DOI: 10.1016/j.stemcr.2024.04.006

Cheng Huang, Haiping Jiang, Jingxi Dong, Liyuan Jiang, Jie Li, Jing Xu, Tongtong Cui, Leyun Wang, Xin Li, Guihai Feng, Ying Zhang, Tianda Li, Wei Li, Qi Zhou

{"title":"Functional mouse hepatocytes derived from interspecies chimeric livers effectively mitigate chronic liver fibrosis.","authors":"Cheng Huang, Haiping Jiang, Jingxi Dong, Liyuan Jiang, Jie Li, Jing Xu, Tongtong Cui, Leyun Wang, Xin Li, Guihai Feng, Ying Zhang, Tianda Li, Wei Li, Qi Zhou","doi":"10.1016/j.stemcr.2024.04.006","DOIUrl":"10.1016/j.stemcr.2024.04.006","url":null,"abstract":"Liver disease is a major global health challenge. There is a shortage of liver donors worldwide, and hepatocyte transplantation (HT) may be an effective treatment to overcome this problem. However, the present approaches for generation of hepatocytes are associated with challenges, and interspecies chimera-derived hepatocytes produced by interspecies blastocyst complementation (IBC) may be promising donor hepatocytes because of their more comprehensive hepatic functions. In this study, we isolated mouse hepatocytes from mouse-rat chimeric livers using IBC and found that interspecies chimera-derived hepatocytes exhibited mature hepatic functions in terms of lipid accumulation, glycogen storage, and urea synthesis. Meanwhile, they were more similar to endogenous hepatocytes than hepatocytes derived in vitro. Interspecies chimera-derived hepatocytes could relieve chronic liver fibrosis and reside in the injured liver after transplantation. Our results suggest that interspecies chimera-derived hepatocytes are a potentially reliable source of hepatocytes and can be applied as a therapeutic approach for HT.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11390683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140905083","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}

引用次数: 0

Human pluripotent stem cell-derived kidney organoids reveal tubular epithelial pathobiology of heterozygous HNF1B-associated dysplastic kidney malformations. 人多能干细胞衍生的肾脏器官组织揭示了杂合子HNF1B相关发育不良肾畸形的肾小管上皮病理生物学。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-06-11 Epub Date: 2024-05-23 DOI: 10.1016/j.stemcr.2024.04.011

Ioannis Bantounas, Kirsty M Rooney, Filipa M Lopes, Faris Tengku, Steven Woods, Leo A H Zeef, I-Hsuan Lin, Shweta Y Kuba, Nicola Bates, Sandra Hummelgaard, Katherine A Hillman, Silvia Cereghini, Adrian S Woolf, Susan J Kimber

{"title":"Human pluripotent stem cell-derived kidney organoids reveal tubular epithelial pathobiology of heterozygous HNF1B-associated dysplastic kidney malformations.","authors":"Ioannis Bantounas, Kirsty M Rooney, Filipa M Lopes, Faris Tengku, Steven Woods, Leo A H Zeef, I-Hsuan Lin, Shweta Y Kuba, Nicola Bates, Sandra Hummelgaard, Katherine A Hillman, Silvia Cereghini, Adrian S Woolf, Susan J Kimber","doi":"10.1016/j.stemcr.2024.04.011","DOIUrl":"10.1016/j.stemcr.2024.04.011","url":null,"abstract":"Hepatocyte nuclear factor 1B (HNF1B) encodes a transcription factor expressed in developing human kidney epithelia. Heterozygous HNF1B mutations are the commonest monogenic cause of dysplastic kidney malformations (DKMs). To understand their pathobiology, we generated heterozygous HNF1B mutant kidney organoids from CRISPR-Cas9 gene-edited human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) reprogrammed from a family with HNF1B-associated DKMs. Mutant organoids contained enlarged malformed tubules displaying deregulated cell turnover. Numerous genes implicated in Mendelian kidney tubulopathies were downregulated, and mutant tubules resisted the cyclic AMP (cAMP)-mediated dilatation seen in controls. Bulk and single-cell RNA sequencing (scRNA-seq) analyses indicated abnormal Wingless/Integrated (WNT), calcium, and glutamatergic pathways, the latter hitherto unstudied in developing kidneys. Glutamate ionotropic receptor kainate type subunit 3 (GRIK3) was upregulated in malformed mutant nephron tubules and prominent in HNF1B mutant fetal human dysplastic kidney epithelia. These results reveal morphological, molecular, and physiological roles for HNF1B in human kidney tubule differentiation and morphogenesis illuminating the developmental origin of mutant-HNF1B-causing kidney disease.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11297557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141093918","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}

引用次数: 0

Reduction of H3K9 methylation by G9a inhibitors improves the development of mouse SCNT embryos. 通过 G9a 抑制剂减少 H3K9 甲基化可改善小鼠 SCNT 胚胎的发育。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-06-11 Epub Date: 2024-05-09 DOI: 10.1016/j.stemcr.2024.04.003

Shogo Matoba, Daiki Shikata, Fumiyuki Shirai, Takaki Tatebe, Michiko Hirose, Akiko Nakata, Naomi Watanabe, Ayumi Hasegawa, Akihiro Ito, Minoru Yoshida, Atsuo Ogura

{"title":"Reduction of H3K9 methylation by G9a inhibitors improves the development of mouse SCNT embryos.","authors":"Shogo Matoba, Daiki Shikata, Fumiyuki Shirai, Takaki Tatebe, Michiko Hirose, Akiko Nakata, Naomi Watanabe, Ayumi Hasegawa, Akihiro Ito, Minoru Yoshida, Atsuo Ogura","doi":"10.1016/j.stemcr.2024.04.003","DOIUrl":"10.1016/j.stemcr.2024.04.003","url":null,"abstract":"Removal of somatic histone H3 lysine 9 trimethylation (H3K9me3) from the embryonic genome can improve the efficiency of mammalian cloning using somatic cell nuclear transfer (SCNT). However, this strategy involves the injection of histone demethylase mRNA into embryos, which is limiting because of its invasive and labor-consuming nature. Here, we report that treatment with an inhibitor of G9a (G9ai), the major histone methyltransferase that introduces H3K9me1/2 in mammals, greatly improved the development of mouse SCNT embryos. Intriguingly, G9ai caused an immediate reduction of H3K9me1/2, a secondary loss of H3K9me3 in SCNT embryos, and increased the birth rate of cloned pups about 5-fold (up to 3.9%). G9ai combined with the histone deacetylase inhibitor trichostatin A further improved this rate to 14.5%. Mechanistically, G9ai and TSA synergistically enhanced H3K9me3 demethylation and boosted zygotic genome activation. Thus, we established an easy, highly effective SCNT protocol that would enhance future cloning research and applications.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11390627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140905087","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}

引用次数: 0

Forced LMX1A expression induces dorsal neural fates and disrupts patterning of human embryonic stem cells into ventral midbrain dopaminergic neurons. 强制表达 LMX1A 可诱导背侧神经命运，并破坏人类胚胎干细胞向腹侧中脑多巴胺能神经元的模式化。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-06-11 Epub Date: 2024-05-16 DOI: 10.1016/j.stemcr.2024.04.010

Pedro Rifes, Janko Kajtez, Josefine Rågård Christiansen, Alrik Schörling, Gaurav Singh Rathore, Daniel A Wolf, Andreas Heuer, Agnete Kirkeby

{"title":"Forced LMX1A expression induces dorsal neural fates and disrupts patterning of human embryonic stem cells into ventral midbrain dopaminergic neurons.","authors":"Pedro Rifes, Janko Kajtez, Josefine Rågård Christiansen, Alrik Schörling, Gaurav Singh Rathore, Daniel A Wolf, Andreas Heuer, Agnete Kirkeby","doi":"10.1016/j.stemcr.2024.04.010","DOIUrl":"10.1016/j.stemcr.2024.04.010","url":null,"abstract":"The differentiation of human pluripotent stem cells into ventral mesencephalic dopaminergic (DA) fate is relevant for the treatment of Parkinson's disease. Shortcuts to obtaining DA cells through direct reprogramming often include forced expression of the transcription factor LMX1A. Although reprogramming with LMX1A can generate tyrosine hydroxylase (TH)-positive cells, their regional identity remains elusive. Using an in vitro model of early human neural tube patterning, we report that forced LMX1A expression induced a ventral-to-dorsal fate shift along the entire neuroaxis with the emergence of roof plate fates despite the presence of ventralizing molecules. The LMX1A-expressing progenitors gave rise to grafts containing roof plate-derived choroid plexus cysts as well as ectopically induced TH-positive neurons of a forebrain identity. Early activation of LMX1A prior to floor plate specification was necessary for the dorsalizing effect. Our work suggests using caution in employing LMX1A for the induction of DA fate, as this factor may generate roof plate rather than midbrain fates.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11390620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140959577","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}

引用次数: 0

In and out: Benchmarking in vitro, in vivo, ex vivo, and xenografting approaches for an integrative brain disease modeling pipeline. 体内和体外：对体外、体内、体外和异种移植方法进行基准测试，以建立综合脑疾病建模管道。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-06-11 DOI: 10.1016/j.stemcr.2024.05.004

Marlene F Pereira, Reinald Shyti, Giuseppe Testa

{"title":"In and out: Benchmarking in vitro, in vivo, ex vivo, and xenografting approaches for an integrative brain disease modeling pipeline.","authors":"Marlene F Pereira, Reinald Shyti, Giuseppe Testa","doi":"10.1016/j.stemcr.2024.05.004","DOIUrl":"10.1016/j.stemcr.2024.05.004","url":null,"abstract":"Human cellular models and their neuronal derivatives have afforded unprecedented advances in elucidating pathogenic mechanisms of neuropsychiatric diseases. Notwithstanding their indispensable contribution, animal models remain the benchmark in neurobiological research. In an attempt to harness the best of both worlds, researchers have increasingly relied on human/animal chimeras by xenografting human cells into the animal brain. Despite the unparalleled potential of xenografting approaches in the study of the human brain, literature resources that systematically examine their significance and advantages are surprisingly lacking. We fill this gap by providing a comprehensive account of brain diseases that were thus far subjected to all three modeling approaches (transgenic rodents, in vitro human lineages, human-animal xenografting) and provide a critical appraisal of the impact of xenografting approaches for advancing our understanding of those diseases and brain development. Next, we give our perspective on integrating xenografting modeling pipeline with recent cutting-edge technological advancements.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11390705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141311794","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}

引用次数: 0

Connie Eaves (1944–2024) 康妮-伊夫（1944-2024）

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-06-01 DOI: 10.1016/j.stemcr.2024.05.003

Nika Shakiba

引用次数: 0

H1FOO-DD promotes efficiency and uniformity in reprogramming to naive pluripotency. H1FOO-DD促进了向幼稚多能性重编程的效率和一致性。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-05-14 Epub Date: 2024-05-02 DOI: 10.1016/j.stemcr.2024.04.005

Akira Kunitomi, Ryoko Hirohata, Mitsujiro Osawa, Kaho Washizu, Vanessa Arreola, Norikazu Saiki, Tomoaki M Kato, Masaki Nomura, Haruko Kunitomi, Tokiko Ohkame, Yusuke Ohkame, Jitsutaro Kawaguchi, Hiroto Hara, Kohji Kusano, Takuya Yamamoto, Yasuhiro Takashima, Shugo Tohyama, Shinsuke Yuasa, Keiichi Fukuda, Naoko Takasu, Shinya Yamanaka

{"title":"H1FOO-DD promotes efficiency and uniformity in reprogramming to naive pluripotency.","authors":"Akira Kunitomi, Ryoko Hirohata, Mitsujiro Osawa, Kaho Washizu, Vanessa Arreola, Norikazu Saiki, Tomoaki M Kato, Masaki Nomura, Haruko Kunitomi, Tokiko Ohkame, Yusuke Ohkame, Jitsutaro Kawaguchi, Hiroto Hara, Kohji Kusano, Takuya Yamamoto, Yasuhiro Takashima, Shugo Tohyama, Shinsuke Yuasa, Keiichi Fukuda, Naoko Takasu, Shinya Yamanaka","doi":"10.1016/j.stemcr.2024.04.005","DOIUrl":"10.1016/j.stemcr.2024.04.005","url":null,"abstract":"Heterogeneity among both primed and naive pluripotent stem cell lines remains a major unresolved problem. Here we show that expressing the maternal-specific linker histone H1FOO fused to a destabilizing domain (H1FOO-DD), together with OCT4, SOX2, KLF4, and LMYC, in human somatic cells improves the quality of reprogramming to both primed and naive pluripotency. H1FOO-DD expression was associated with altered chromatin accessibility around pluripotency genes and with suppression of the innate immune response. Notably, H1FOO-DD generates naive induced pluripotent stem cells with lower variation in transcriptome and methylome among clones and a more uniform and superior differentiation potency. Furthermore, we elucidated that upregulation of FKBP1A, driven by these five factors, plays a key role in H1FOO-DD-mediated reprogramming.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11103934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140851314","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}

引用次数: 0

MAGIK: A rapid and efficient method to create lineage-specific reporters in human pluripotent stem cells. MAGIK：在人类多能干细胞中创建系特异性报告的快速高效方法。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-05-14 Epub Date: 2024-04-04 DOI: 10.1016/j.stemcr.2024.03.005

Tahir Haideri, Jirong Lin, Xiaoping Bao, Xiaojun Lance Lian

{"title":"MAGIK: A rapid and efficient method to create lineage-specific reporters in human pluripotent stem cells.","authors":"Tahir Haideri, Jirong Lin, Xiaoping Bao, Xiaojun Lance Lian","doi":"10.1016/j.stemcr.2024.03.005","DOIUrl":"10.1016/j.stemcr.2024.03.005","url":null,"abstract":"Precise insertion of fluorescent proteins into lineage-specific genes in human pluripotent stem cells (hPSCs) presents challenges due to low knockin efficiency and difficulties in isolating targeted cells. To overcome these hurdles, we present the modified mRNA (ModRNA)-based Activation for Gene Insertion and Knockin (MAGIK) method. MAGIK operates in two steps: first, it uses a Cas9-2A-p53DD modRNA with a mini-donor plasmid (without a drug selection cassette) to significantly enhance efficiency. Second, a deactivated Cas9 activator modRNA and a 'dead' guide RNA are used to temporarily activate the targeted gene, allowing for live cell sorting of targeted cells. Consequently, MAGIK eliminates the need for drug selection cassettes or labor-intensive single-cell colony screening, expediting precise gene editing. We showed MAGIK can be utilized to insert fluorescent proteins into various genes, including SOX17, NKX6.1, NKX2.5, and PDX1, across multiple hPSC lines. This underscores its robust performance and offers a promising solution for achieving knockin in hPSCs within a significantly shortened time frame.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11103783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140860083","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}

引用次数: 0

Identification of unapproved orthopedic regenerative medicine: Usefulness of the Act on Safety of Regenerative Medicine. 识别未经批准的骨科再生药物：再生医学安全法》的作用。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-05-14 Epub Date: 2024-05-02 DOI: 10.1016/j.stemcr.2024.04.001

Yuichiro Ukon, Satoshi Hosoya, Kazuki Morita, Yuji Yokozeki, Tomoko Kataoka, Takayuki Kitahara, Hirokazu Mae, Yuya Kanie, Masayuki Furuya, Takahito Fujimori, Takashi Kaito, Kiyoshi Okada, Akira Myoui, Seiji Okada

引用次数: 0