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  1. AU="Daniel Paull"
  2. AU="H Divecha"
  3. AU="Chetata, Nabil"
  4. AU="Zuo, Nan"
  5. AU="Lin, Raymond Tzer-Pin"
  6. AU="Whittington, Karen B"
  7. AU="Beutel, Gernot"
  8. AU="Koh, Siang Boon"
  9. AU="Rajki, Anikó"
  10. AU="Polina B. Drozdova"
  11. AU=Zhang Xiuhong AU=Zhang Xiuhong
  12. AU=Hauer Julia
  13. AU="Widiasih, Natalia"
  14. AU="Besnik Bajrami"
  15. AU=Mazza Mario Gennaro
  16. AU="Kwong, A S K"
  17. AU="Hadian, Marziye"
  18. AU="Chen, Yaying"
  19. AU="Ortega, Francisco B"
  20. AU=Cobb Samuel N
  21. AU="Abdelmohssin El Mokaddem"
  22. AU="Iwao Ojima"
  23. AU="Abazi, Sokol"
  24. AU="Cook, Rebecca"
  25. AU=Martin Flavius
  26. AU="Cipriani, Raffaela"
  27. AU="Levin, Michael E."
  28. AU="Yang, Dayu"

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  1. Artikel ; Online: FocA

    Jeff Winchell / Gabriel Comolet / Geoff Buckley-Herd / Dillion Hutson / Neeloy Bose / Daniel Paull / Bianca Migliori

    SLAS Discovery, Vol 28, Iss 7, Pp 306-

    A deep learning tool for reliable, near-real-time imaging focus analysis in automated cell assay pipelines

    2023  Band 315

    Abstract: The increasing use of automation in cellular assays and cell culture presents significant opportunities to enhance the scale and throughput of imaging assays, but to do so, reliable data quality and consistency are critical. Realizing the full potential ... ...

    Abstract The increasing use of automation in cellular assays and cell culture presents significant opportunities to enhance the scale and throughput of imaging assays, but to do so, reliable data quality and consistency are critical. Realizing the full potential of automation will thus require the design of robust analysis pipelines that span the entire workflow in question. Here we present FocA, a deep learning tool that, in near real-time, identifies in-focus and out-of-focus images generated on a fully automated cell biology research platform, the NYSCF Global Stem Cell Array®. The tool is trained on small patches of downsampled images to maximize computational efficiency without compromising accuracy, and optimized to make sure no sub-quality images are stored and used in downstream analyses. The tool automatically generates balanced and maximally diverse training sets to avoid bias. The resulting model correctly identifies 100% of out-of-focus and 98% of in-focus images in under 4 s per 96-well plate, and achieves this result even in heavily downsampled data (∼30 times smaller than native resolution). Integrating the tool into automated workflows minimizes the need for human verification as well as the collection and usage of low-quality data. FocA thus offers a solution to ensure reliable image data hygiene and improve the efficiency of automated imaging workflows using minimal computational resources.
    Schlagwörter Machine learning ; Automation ; Robotics ; Focus analysis ; Cell culture ; Cell assays ; Medicine (General) ; R5-920 ; Biotechnology ; TP248.13-248.65
    Thema/Rubrik (Code) 670
    Sprache Englisch
    Erscheinungsdatum 2023-10-01T00:00:00Z
    Verlag Elsevier
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  2. Artikel ; Online: Isogenic human trophectoderm cells demonstrate the role of NDUFA4 and associated variants in ZIKV infection

    Liuliu Yang / Yuling Han / Ting Zhou / Lauretta A. Lacko / Mohsan Saeed / Christina Tan / Ron Danziger / Jiajun Zhu / Zeping Zhao / Clare Cahir / Alice Maria Giani / Yang Li / Xue Dong / Dorota Moroziewicz / Daniel Paull / Zhengming Chen / Aaron Zhong / Scott A. Noggle / Charles M. Rice /
    Qibin Qi / Todd Evans / Shuibing Chen

    iScience, Vol 26, Iss 7, Pp 107001- (2023)

    2023  

    Abstract: Summary: Population-based genome-wide association studies (GWAS) normally require a large sample size, which can be labor intensive and costly. Recently, we reported a human induced pluripotent stem cell (hiPSC) array-based GWAS method, identifying ... ...

    Abstract Summary: Population-based genome-wide association studies (GWAS) normally require a large sample size, which can be labor intensive and costly. Recently, we reported a human induced pluripotent stem cell (hiPSC) array-based GWAS method, identifying NDUFA4 as a host factor for Zika virus (ZIKV) infection. In this study, we extended our analysis to trophectoderm cells, which constitute one of the major routes of mother-to-fetus transmission of ZIKV during pregnancy. We differentiated hiPSCs from various donors into trophectoderm cells. We then infected cells carrying loss of function mutations in NDUFA4, harboring risk versus non-risk alleles of SNPs (rs917172 and rs12386620) or having deletions in the NDUFA4 cis-regulatory region with ZIKV. We found that loss/reduction of NDUFA4 suppressed ZIKV infection in trophectoderm cells. This study validated our published hiPSC array-based system as a useful platform for GWAS and confirmed the role of NDUFA4 as a susceptibility locus for ZIKV in disease-relevant trophectoderm cells.
    Schlagwörter Stem cells research ; Virology ; Science ; Q
    Thema/Rubrik (Code) 570
    Sprache Englisch
    Erscheinungsdatum 2023-07-01T00:00:00Z
    Verlag Elsevier
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  3. Artikel ; Online: Derivation and characterization of the NIH registry human stem cell line NYSCF101 under defined feeder-free conditions

    Ana Sevilla / Eliana Forero / Matthew Zimmer / Hector Martinez / Katie Reggio / Daniel Paull / Dieter Egli / Scott Noggle

    Stem Cell Research, Vol 29, Iss , Pp 197-

    2018  Band 201

    Abstract: The human embryonic stem cell line NYSCFe002-A was derived from a day 6 blastocyst in feeder-free and antibiotic free conditions. The blastocyst was voluntarily donated for research as surplus after in vitro fertilization treatment following informed ... ...

    Abstract The human embryonic stem cell line NYSCFe002-A was derived from a day 6 blastocyst in feeder-free and antibiotic free conditions. The blastocyst was voluntarily donated for research as surplus after in vitro fertilization treatment following informed consent. The NYSCFe002-A line expresses all the pluripotency markers and has the potential to differentiate into all three germ layers in vitro. The line presents normal karyotype and is mycoplasma free. This line is registered as NYSCF101 on the NIH Registry.
    Schlagwörter Biology (General) ; QH301-705.5
    Sprache Englisch
    Erscheinungsdatum 2018-05-01T00:00:00Z
    Verlag Elsevier
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  4. Artikel ; Online: Stem cell‐derived retinal pigment epithelium from patients with age‐related macular degeneration exhibit reduced metabolism and matrix interactions

    Jie Gong / Hui Cai / NYSCF Global Stem Cell Array Team / Scott Noggle / Daniel Paull / Lawrence J. Rizzolo / Lucian V. Del Priore / Mark A. Fields

    Stem Cells Translational Medicine, Vol 9, Iss 3, Pp 364-

    2020  Band 376

    Abstract: Abstract Modeling age‐related macular degeneration (AMD) is challenging, because it is a multifactorial disease. To focus on interactions between the retinal pigment epithelium (RPE) and Bruch's membrane, we generated RPE from AMD patients and used an ... ...

    Abstract Abstract Modeling age‐related macular degeneration (AMD) is challenging, because it is a multifactorial disease. To focus on interactions between the retinal pigment epithelium (RPE) and Bruch's membrane, we generated RPE from AMD patients and used an altered extracellular matrix (ECM) that models aged Bruch's membrane. Induced pluripotent stem cells (iPSCs) were generated from fibroblasts isolated from AMD patients or age‐matched (normal) controls. RPE derived from iPSCs were analyzed by morphology, marker expression, transepithelial electrical resistance (TER), and phagocytosis of rod photoreceptor outer segments. Cell attachment and viability was tested on nitrite‐modified ECM, a typical modification of aged Bruch's membrane. DNA microarrays with hierarchical clustering and analysis of mitochondrial function were used to elucidate possible mechanisms for the observed phenotypes. Differentiated RPE displayed cell‐specific morphology and markers. The TER and phagocytic capacity were similar among iPSC‐derived RPE cultures. However, distinct clusters were found for the transcriptomes of AMD and control iPSC‐derived RPE. AMD‐derived iPSC‐RPE downregulated genes responsible for metabolic‐related pathways and cell attachment. AMD‐derived iPSC‐RPE exhibited reduced mitochondrial respiration and ability to attach and survive on nitrite‐modified ECM. Cells that did attach induced the expression of complement genes. Despite reprogramming, iPSC derived from AMD patients yielded RPE with a transcriptome that is distinct from that of age‐matched controls. When challenged with an AMD‐like modification of Bruch's membrane, AMD‐derived iPSC‐RPE activated the complement immune system.
    Schlagwörter age‐related macular degeneration ; aging ; Bruch's membrane ; induced pluripotent stem cells ; nonenzymatic nitration ; retinal pigment epithelium ; Medicine (General) ; R5-920 ; Cytology ; QH573-671
    Thema/Rubrik (Code) 571
    Sprache Englisch
    Erscheinungsdatum 2020-03-01T00:00:00Z
    Verlag Oxford University Press
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  5. Artikel ; Online: A dual SHOX2:GFP; MYH6:mCherry knockin hESC reporter line for derivation of human SAN-like cells

    Zaniar Ghazizadeh / Jiajun Zhu / Faranak Fattahi / Alice Tang / Xiaolu Sun / Sadaf Amin / Su-Yi Tsai / Mona Khalaj / Ting Zhou / Ryan M. Samuel / Tuo Zhang / Francis A. Ortega / Miriam Gordillo / Dorota Moroziewicz / Daniel Paull / Scott A. Noggle / Jenny Zhaoying Xiang / Lorenz Studer / David J. Christini /
    Geoffrey S. Pitt / Todd Evans / Shuibing Chen

    iScience, Vol 25, Iss 4, Pp 104153- (2022)

    2022  

    Abstract: Summary: The sinoatrial node (SAN) is the primary pacemaker of the heart. The human SAN is poorly understood due to limited primary tissue access and limitations in robust in vitro derivation methods. We developed a dual SHOX2:GFP; MYH6:mCherry knockin ... ...

    Abstract Summary: The sinoatrial node (SAN) is the primary pacemaker of the heart. The human SAN is poorly understood due to limited primary tissue access and limitations in robust in vitro derivation methods. We developed a dual SHOX2:GFP; MYH6:mCherry knockin human embryonic stem cell (hESC) reporter line, which allows the identification and purification of SAN-like cells. Using this line, we performed several rounds of chemical screens and developed an efficient strategy to generate and purify hESC-derived SAN-like cells (hESC-SAN). The derived hESC-SAN cells display molecular and electrophysiological characteristics of bona fide nodal cells, which allowed exploration of their transcriptional profile at single-cell level. In sum, our dual reporter system facilitated an effective strategy for deriving human SAN-like cells, which can potentially be used for future disease modeling and drug discovery.
    Schlagwörter Biological sciences ; Stem cells research ; Methodology in biological sciences ; Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2022-04-01T00:00:00Z
    Verlag Elsevier
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  6. Artikel ; Online: Derivation and characterization of the NYSCFe003-A human embryonic stem cell line

    Ana Sevilla / Eliana Forero / Matthew Zimmer / Hector Martinez / Katie Reggio / Daniel Paull / Dieter Egli / Scott Noggle

    Stem Cell Research, Vol 25, Iss C, Pp 217-

    2017  Band 220

    Abstract: The human embryonic stem cell line NYSCFe003-A was derived from a day 5 to day 6 blastocyst in feeder-free and antibiotic free conditions. The blastocyst was voluntarily donated for research as surplus after in vitro fertilization treatment following ... ...

    Abstract The human embryonic stem cell line NYSCFe003-A was derived from a day 5 to day 6 blastocyst in feeder-free and antibiotic free conditions. The blastocyst was voluntarily donated for research as surplus after in vitro fertilization treatment following informed consent. The NYSCFe003-A line expresses all the pluripotency markers and has the potential to differentiate into all three germ layers in vitro. The line presents normal karyotype and is mycoplasma free.
    Schlagwörter Biology (General) ; QH301-705.5
    Sprache Englisch
    Erscheinungsdatum 2017-12-01T00:00:00Z
    Verlag Elsevier
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  7. Artikel ; Online: Integrating deep learning and unbiased automated high-content screening to identify complex disease signatures in human fibroblasts

    Lauren Schiff / Bianca Migliori / Ye Chen / Deidre Carter / Caitlyn Bonilla / Jenna Hall / Minjie Fan / Edmund Tam / Sara Ahadi / Brodie Fischbacher / Anton Geraschenko / Christopher J. Hunter / Subhashini Venugopalan / Sean DesMarteau / Arunachalam Narayanaswamy / Selwyn Jacob / Zan Armstrong / Peter Ferrarotto / Brian Williams /
    Geoff Buckley-Herd / Jon Hazard / Jordan Goldberg / Marc Coram / Reid Otto / Edward A. Baltz / Laura Andres-Martin / Orion Pritchard / Alyssa Duren-Lubanski / Ameya Daigavane / Kathryn Reggio / NYSCF Global Stem Cell Array® Team / Phillip C. Nelson / Michael Frumkin / Susan L. Solomon / Lauren Bauer / Raeka S. Aiyar / Elizabeth Schwarzbach / Scott A. Noggle / Frederick J. Monsma / Daniel Paull / Marc Berndl / Samuel J. Yang / Bjarki Johannesson

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Band 13

    Abstract: By coupling robotic cell culture systems with artificial intelligence–powered image analysis, Schiff et al. identify previously unseen characteristics of Parkinson’s disease in patient skin cells that distinguish them from healthy controls. ...

    Abstract By coupling robotic cell culture systems with artificial intelligence–powered image analysis, Schiff et al. identify previously unseen characteristics of Parkinson’s disease in patient skin cells that distinguish them from healthy controls.
    Schlagwörter Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2022-03-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  8. Artikel ; Online: Improved methods for reprogramming human dermal fibroblasts using fluorescence activated cell sorting.

    David J Kahler / Faizzan S Ahmad / Anita Ritz / Haiqing Hua / Dorota N Moroziewicz / Andrew A Sproul / Carmen R Dusenberry / Linshan Shang / Daniel Paull / Matthew Zimmer / Keren A Weiss / Dieter Egli / Scott A Noggle

    PLoS ONE, Vol 8, Iss 3, p e

    2013  Band 59867

    Abstract: Current methods to derive induced pluripotent stem cell (iPSC) lines from human dermal fibroblasts by viral infection rely on expensive and lengthy protocols. One major factor contributing to the time required to derive lines is the ability of ... ...

    Abstract Current methods to derive induced pluripotent stem cell (iPSC) lines from human dermal fibroblasts by viral infection rely on expensive and lengthy protocols. One major factor contributing to the time required to derive lines is the ability of researchers to identify fully reprogrammed unique candidate clones from a mixed cell population containing transformed or partially reprogrammed cells and fibroblasts at an early time point post infection. Failure to select high quality colonies early in the derivation process results in cell lines that require increased maintenance and unreliable experimental outcomes. Here, we describe an improved method for the derivation of iPSC lines using fluorescence activated cell sorting (FACS) to isolate single cells expressing the cell surface marker signature CD13(NEG)SSEA4(POS)Tra-1-60(POS) on day 7-10 after infection. This technique prospectively isolates fully reprogrammed iPSCs, and depletes both parental and "contaminating" partially reprogrammed fibroblasts, thereby substantially reducing the time and reagents required to generate iPSC lines without the use of defined small molecule cocktails. FACS derived iPSC lines express common markers of pluripotency, and possess spontaneous differentiation potential in vitro and in vivo. To demonstrate the suitability of FACS for high-throughput iPSC generation, we derived 228 individual iPSC lines using either integrating (retroviral) or non- integrating (Sendai virus) reprogramming vectors and performed extensive characterization on a subset of those lines. The iPSC lines used in this study were derived from 76 unique samples from a variety of tissue sources, including fresh or frozen fibroblasts generated from biopsies harvested from healthy or disease patients.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 616
    Sprache Englisch
    Erscheinungsdatum 2013-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  9. Artikel ; Online: iPSC-Derived Dopamine Neurons Reveal Differences between Monozygotic Twins Discordant for Parkinson’s Disease

    Chris M. Woodard / Brian A. Campos / Sheng-Han Kuo / Melissa J. Nirenberg / Michael W. Nestor / Matthew Zimmer / Eugene V. Mosharov / David Sulzer / Hongyan Zhou / Daniel Paull / Lorraine Clark / Eric E. Schadt / Sergio Pablo Sardi / Lee Rubin / Kevin Eggan / Mathew Brock / Scott Lipnick / Mahendra Rao / Stephen Chang /
    Aiqun Li / Scott A. Noggle

    Cell Reports, Vol 9, Iss 4, Pp 1173-

    2014  Band 1182

    Abstract: Parkinson’s disease (PD) has been attributed to a combination of genetic and nongenetic factors. We studied a set of monozygotic twins harboring the heterozygous glucocerebrosidase mutation (GBA N370S) but clinically discordant for PD. We applied induced ...

    Abstract Parkinson’s disease (PD) has been attributed to a combination of genetic and nongenetic factors. We studied a set of monozygotic twins harboring the heterozygous glucocerebrosidase mutation (GBA N370S) but clinically discordant for PD. We applied induced pluripotent stem cell (iPSC) technology for PD disease modeling using the twins’ fibroblasts to evaluate and dissect the genetic and nongenetic contributions. Utilizing fluorescence-activated cell sorting, we obtained a homogenous population of “footprint-free” iPSC-derived midbrain dopaminergic (mDA) neurons. The mDA neurons from both twins had ∼50% GBA enzymatic activity, ∼3-fold elevated α-synuclein protein levels, and a reduced capacity to synthesize and release dopamine. Interestingly, the affected twin’s neurons showed an even lower dopamine level, increased monoamine oxidase B (MAO-B) expression, and impaired intrinsic network activity. Overexpression of wild-type GBA and treatment with MAO-B inhibitors normalized α-synuclein and dopamine levels, suggesting a combination therapy for the affected twin.
    Schlagwörter Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 571
    Sprache Englisch
    Erscheinungsdatum 2014-11-01T00:00:00Z
    Verlag Elsevier
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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