Pub Date : 2024-11-08DOI: 10.1038/s41592-024-02480-7
Jourdan K Ewoldt, Samuel J DePalma, Maggie E Jewett, M Çağatay Karakan, Yih-Mei Lin, Paria Mir Hashemian, Xining Gao, Lihua Lou, Micheal A McLellan, Jonathan Tabares, Marshall Ma, Adriana C Salazar Coariti, Jin He, Kimani C Toussaint, Thomas G Bifano, Sharan Ramaswamy, Alice E White, Arvind Agarwal, Emma Lejeune, Brendon M Baker, Christopher S Chen
Recent innovations in differentiating cardiomyocytes from human induced pluripotent stem cells (hiPSCs) have unlocked a viable path to creating in vitro cardiac models. Currently, hiPSC-derived cardiomyocytes (hiPSC-CMs) remain immature, leading many in the field to explore approaches to enhance cell and tissue maturation. Here, we systematically analyzed 300 studies using hiPSC-CM models to determine common fabrication, maturation and assessment techniques used to evaluate cardiomyocyte functionality and maturity and compiled the data into an open-access database. Based on this analysis, we present the diversity of, and current trends in, in vitro models and highlight the most common and promising practices for functional assessments. We further analyzed outputs spanning structural maturity, contractile function, electrophysiology and gene expression and note field-wide improvements over time. Finally, we discuss opportunities to collectively pursue the shared goal of hiPSC-CM model development, maturation and assessment that we believe are critical for engineering mature cardiac tissue.
{"title":"Induced pluripotent stem cell-derived cardiomyocyte in vitro models: benchmarking progress and ongoing challenges.","authors":"Jourdan K Ewoldt, Samuel J DePalma, Maggie E Jewett, M Çağatay Karakan, Yih-Mei Lin, Paria Mir Hashemian, Xining Gao, Lihua Lou, Micheal A McLellan, Jonathan Tabares, Marshall Ma, Adriana C Salazar Coariti, Jin He, Kimani C Toussaint, Thomas G Bifano, Sharan Ramaswamy, Alice E White, Arvind Agarwal, Emma Lejeune, Brendon M Baker, Christopher S Chen","doi":"10.1038/s41592-024-02480-7","DOIUrl":"https://doi.org/10.1038/s41592-024-02480-7","url":null,"abstract":"<p><p>Recent innovations in differentiating cardiomyocytes from human induced pluripotent stem cells (hiPSCs) have unlocked a viable path to creating in vitro cardiac models. Currently, hiPSC-derived cardiomyocytes (hiPSC-CMs) remain immature, leading many in the field to explore approaches to enhance cell and tissue maturation. Here, we systematically analyzed 300 studies using hiPSC-CM models to determine common fabrication, maturation and assessment techniques used to evaluate cardiomyocyte functionality and maturity and compiled the data into an open-access database. Based on this analysis, we present the diversity of, and current trends in, in vitro models and highlight the most common and promising practices for functional assessments. We further analyzed outputs spanning structural maturity, contractile function, electrophysiology and gene expression and note field-wide improvements over time. Finally, we discuss opportunities to collectively pursue the shared goal of hiPSC-CM model development, maturation and assessment that we believe are critical for engineering mature cardiac tissue.</p>","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":" ","pages":""},"PeriodicalIF":36.1,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-07DOI: 10.1038/s41592-024-02489-y
Michael Eisenstein
A new generation of increasingly powerful magnets is dramatically extending the resolution, speed and analytical capabilities of magnetic resonance imaging for brain research.
新一代磁力越来越强的磁铁大大提高了脑研究磁共振成像的分辨率、速度和分析能力。
{"title":"Pushing the limits of MRI brain imaging","authors":"Michael Eisenstein","doi":"10.1038/s41592-024-02489-y","DOIUrl":"10.1038/s41592-024-02489-y","url":null,"abstract":"A new generation of increasingly powerful magnets is dramatically extending the resolution, speed and analytical capabilities of magnetic resonance imaging for brain research.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"21 11","pages":"1975-1979"},"PeriodicalIF":36.1,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41592-024-02489-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142595676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-07DOI: 10.1038/s41592-024-02485-2
Lorenz A. Fenk, Felix Baier, Gilles Laurent
The Australian bearded dragon is so called for its distinctive ‘beard’ of spiky scales that can darken and expand during social and defensive displays. This lizard has become a reptilian model system to study the evolution, function and dynamics of neurons and neural circuits (including during sleep) in the amniote brain.
{"title":"The bearded dragon Pogona vitticeps","authors":"Lorenz A. Fenk, Felix Baier, Gilles Laurent","doi":"10.1038/s41592-024-02485-2","DOIUrl":"10.1038/s41592-024-02485-2","url":null,"abstract":"The Australian bearded dragon is so called for its distinctive ‘beard’ of spiky scales that can darken and expand during social and defensive displays. This lizard has become a reptilian model system to study the evolution, function and dynamics of neurons and neural circuits (including during sleep) in the amniote brain.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"21 11","pages":"1964-1966"},"PeriodicalIF":36.1,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142595732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-07DOI: 10.1038/s41592-024-02509-x
Arunima Singh
{"title":"Multi-pass nanopore for single-molecule protein sequencing","authors":"Arunima Singh","doi":"10.1038/s41592-024-02509-x","DOIUrl":"10.1038/s41592-024-02509-x","url":null,"abstract":"","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"21 11","pages":"1974-1974"},"PeriodicalIF":36.1,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142595714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-07DOI: 10.1038/s41592-024-02531-z
With a pictorial Editorial this month, we celebrate the beauty of microscopy images.
通过本月的图片编辑，我们赞美显微图像之美。
{"title":"Microscopic art","authors":"","doi":"10.1038/s41592-024-02531-z","DOIUrl":"10.1038/s41592-024-02531-z","url":null,"abstract":"With a pictorial Editorial this month, we celebrate the beauty of microscopy images.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"21 11","pages":"1961-1961"},"PeriodicalIF":36.1,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41592-024-02531-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142595733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-31DOI: 10.1038/s41592-024-02478-1
Milan Avila Clasen, Max Ruwolt, Cong Wang, Julia Ruta, Boris Bogdanow, Louise U Kurt, Zehong Zhang, Shuai Wang, Fabio C Gozzo, Tao Chen, Paulo C Carvalho, Diogo Borges Lima, Fan Liu
Advancing data analysis tools for proteome-wide cross-linking mass spectrometry (XL-MS) requires ground-truth standards that mimic biological complexity. Here we develop well-controlled XL-MS standards comprising hundreds of recombinant proteins that are systematically mixed for cross-linking. We use one standard dataset to guide the development of Scout, a search engine for XL-MS with MS-cleavable cross-linkers. Using other, independent standard datasets and published datasets, we benchmark the performance of Scout and existing XL-MS software. We find that Scout offers an excellent combination of speed, sensitivity and false discovery rate control. The results illustrate how our large recombinant standard can support the development of XL-MS analysis tools and evaluation of XL-MS results.
{"title":"Proteome-scale recombinant standards and a robust high-speed search engine to advance cross-linking MS-based interactomics.","authors":"Milan Avila Clasen, Max Ruwolt, Cong Wang, Julia Ruta, Boris Bogdanow, Louise U Kurt, Zehong Zhang, Shuai Wang, Fabio C Gozzo, Tao Chen, Paulo C Carvalho, Diogo Borges Lima, Fan Liu","doi":"10.1038/s41592-024-02478-1","DOIUrl":"https://doi.org/10.1038/s41592-024-02478-1","url":null,"abstract":"<p><p>Advancing data analysis tools for proteome-wide cross-linking mass spectrometry (XL-MS) requires ground-truth standards that mimic biological complexity. Here we develop well-controlled XL-MS standards comprising hundreds of recombinant proteins that are systematically mixed for cross-linking. We use one standard dataset to guide the development of Scout, a search engine for XL-MS with MS-cleavable cross-linkers. Using other, independent standard datasets and published datasets, we benchmark the performance of Scout and existing XL-MS software. We find that Scout offers an excellent combination of speed, sensitivity and false discovery rate control. The results illustrate how our large recombinant standard can support the development of XL-MS analysis tools and evaluation of XL-MS results.</p>","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":" ","pages":""},"PeriodicalIF":36.1,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-31DOI: 10.1038/s41592-024-02471-8
Alex R Lederer, Maxine Leonardi, Lorenzo Talamanca, Daniil M Bobrovskiy, Antonio Herrera, Colas Droin, Irina Khven, Hugo J F Carvalho, Alessandro Valente, Albert Dominguez Mantes, Pau Mulet Arabí, Luca Pinello, Felix Naef, Gioele La Manno
Across biological systems, cells undergo coordinated changes in gene expression, resulting in transcriptome dynamics that unfold within a low-dimensional manifold. While low-dimensional dynamics can be extracted using RNA velocity, these algorithms can be fragile and rely on heuristics lacking statistical control. Moreover, the estimated vector field is not dynamically consistent with the traversed gene expression manifold. To address these challenges, we introduce a Bayesian model of RNA velocity that couples velocity field and manifold estimation in a reformulated, unified framework, identifying the parameters of an explicit dynamical system. Focusing on the cell cycle, we implement VeloCycle to study gene regulation dynamics on one-dimensional periodic manifolds and validate its ability to infer cell cycle periods using live imaging. We also apply VeloCycle to reveal speed differences in regionally defined progenitors and Perturb-seq gene knockdowns. Overall, VeloCycle expands the single-cell RNA sequencing analysis toolkit with a modular and statistically consistent RNA velocity inference framework.
{"title":"Statistical inference with a manifold-constrained RNA velocity model uncovers cell cycle speed modulations.","authors":"Alex R Lederer, Maxine Leonardi, Lorenzo Talamanca, Daniil M Bobrovskiy, Antonio Herrera, Colas Droin, Irina Khven, Hugo J F Carvalho, Alessandro Valente, Albert Dominguez Mantes, Pau Mulet Arabí, Luca Pinello, Felix Naef, Gioele La Manno","doi":"10.1038/s41592-024-02471-8","DOIUrl":"10.1038/s41592-024-02471-8","url":null,"abstract":"<p><p>Across biological systems, cells undergo coordinated changes in gene expression, resulting in transcriptome dynamics that unfold within a low-dimensional manifold. While low-dimensional dynamics can be extracted using RNA velocity, these algorithms can be fragile and rely on heuristics lacking statistical control. Moreover, the estimated vector field is not dynamically consistent with the traversed gene expression manifold. To address these challenges, we introduce a Bayesian model of RNA velocity that couples velocity field and manifold estimation in a reformulated, unified framework, identifying the parameters of an explicit dynamical system. Focusing on the cell cycle, we implement VeloCycle to study gene regulation dynamics on one-dimensional periodic manifolds and validate its ability to infer cell cycle periods using live imaging. We also apply VeloCycle to reveal speed differences in regionally defined progenitors and Perturb-seq gene knockdowns. Overall, VeloCycle expands the single-cell RNA sequencing analysis toolkit with a modular and statistically consistent RNA velocity inference framework.</p>","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":" ","pages":""},"PeriodicalIF":36.1,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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