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The DOI matches its Crossref record, with a small difference in title or year; 14 of the 14 references it cites were found in a registry or an index.

Integrated Manufacturing Platform for Cortical Organoids Reveals Early Phosphatase and Prefoldin Dysregulation in MAPT V337M Neurons

Bertucci, Taylor, Bowles, Kathryn R., Lotz, Steven, Bheda, Shiraz, Qi, Le, Farjood, Farhad, Whitton, Katherine, Goderie, Susan K., Borden, Susan, Rossi, Amelia, Tubbesing, Kate, Pedicone, Chiara, Oja, Laura Maria, Lane, Keith, Lotz, Ryan, Lotz, Hailey, Huber, Jack, Chowdhury, Rebecca, Joy, Shona, Miller, Michael, Butler, David C., Arduini, Brigitte L., Murray, Heide F B, Sandhof, Carl Alexander, Silva, M. Catarina, Haggarty, Stephen J., Dony, Leander, Theis, Fabian J., Treutlein, Barbara, Karch, Celeste M., Geschwind, Daniel H., Goate, Alison M., Stern, Jeffrey, Temple, Sally·2023
DOI 10.1101/2023.07.11.548571
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Abstract

Summary: Human pluripotent stem cell (hPSC)-derived cortical organoids are powerful models but are often limited by low efficiency, variability, and stress-related artifacts. To address these challenges, we developed a scalable organoid platform with end-to-end quality control (QC) metrics spanning manufacturing and single-cell RNA-sequencing (scRNA-seq), developed using eight MAPT mutation isogenic line sets relevant to frontotemporal dementia (FTD-tau). Using a 96 slit-well format, we achieved ∼100% production efficiency across 64 lines. Controlled-release FGF2 enhanced iPSC pluripotency and reduced mesendodermal contaminants, while optimized SB431542 dosing enhanced cortical patterning across lines with variable TGFBR1/ALK5 expression. The resulting organoids displayed transcriptomic profiles and low-stress signatures closely aligned with the developing human cortex. Applying a cortical organoid scRNA-seq index (CortiCOSI), we identified early dysregulation of phosphatase regulators ( PPP2CA, ANP32A ) and the prefoldin subunit PFDN6 in MAPT V337M excitatory neurons before tau hyperphosphorylation and oligomerization. This platform improves scalability, reproducibility, and mechanistic insight in cortical organoid studies.

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    From GRAMD1B is a regulator of lipid homeostasis, autophagic flux and phosphorylated tau (2025) · cites this paper as [96]

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    “Recent advances using the AggreWell™800 Microwell or similar culture plates have provided easy and reproducible production of HNOs96.”

    From GRAMD1B is a regulator of lipid homeostasis, autophagic flux and phosphorylated tau (2025) · cites this paper as [96]

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Metadata

Authors
Bertucci, T., Bowles, K. R., Lotz, S., Bheda, S., Qi, L., Farjood, F., Whitton, K., Goderie, S. K., Borden, S., Rossi, A., Tubbesing, K., Pedicone, C., Oja, L. M., Lane, K., Lotz, R., Lotz, H., Huber, J., Chowdhury, R., Joy, S., Miller, M., Butler, D. C., Arduini, B. L., Murray, H. F. B., Sandhof, C. A., Silva, M. C., Haggarty, S. J., Dony, L., Theis, F. J., Treutlein, B., Karch, C. M., Geschwind, D. H., Goate, A. M., Stern, J., & Temple, S.
Affiliations
  • Neural Stem Cell Institute, 150 New Scotland Avenue, Albany, NY 12208
  • UK Dementia Research Institute at the University of Edinburgh, Edinburgh Bioquarter, Edinburgh, UK, EH16 4SB
  • Program in Neurogenetics, Department of Neurology, and Department of Human Genetics David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
  • Dipatrimento di Neuroscienze sperimentali, IRCCS Azienda ospedaliera metropolitana, Policlinico San Martino, Genova, Italy
  • Dept. of Genetics & Genomic Sciences, Ronald M. Loeb Center for Alzheimer’s disease, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029
  • Department of Neurology, Chemical Neurobiology Laboratory, Center for Genomic Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA
  • Institute of Computational Biology, Computational Health Center, Helmholtz Munich, Neuherberg, Germany
  • Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland
  • Department of Psychiatry, Knight Alzheimer Disease Research Center, Washington University in St Louis, St Louis, MO, USA
ORCID
Publisher
openRxiv
Published
2023-07-11
DOI
10.1101/2023.07.11.548571
Cited by
22
References
14
Type
Preprint
Licence
www.biorxiv.org/about/FAQ#license (vor)
Funders
  • NIH (R35NS097277, U01AG072464, 1R01NS142335, RF1NS123568, U54NS123746, U19AG069701)
  • The Rainwater Charitable Foundation and the Tau Consortium
  • Association for Frontotemporal Degeneration
  • BrightFocus Foundation
  • UK Dementia Research Institute [UKDRI-4211] through UK DRI Ltd, principally funded by the Medical Research Council
  • Massachusetts Center for Alzheimer’s Therapeutics Science

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