@misc{6995,
  abstract     = {Human brain organoids represent a powerful tool for the study of human neurological diseases particularly those that impact brain growth and structure. However, many neurological diseases lack obvious anatomical abnormalities, yet significantly impact neural network functions, raising the question of whether organoids possess sufficient neural network architecture and complexity to model these conditions. Here, we explore the network level functions of brain organoids using calcium sensor imaging and extracellular recording approaches that together reveal the existence of complex oscillatory network behaviors reminiscent of intact brain preparations. We further demonstrate strikingly abnormal epileptiform network activity in organoids derived from a Rett Syndrome patient despite only modest anatomical differences from isogenically matched controls, and rescue with an unconventional neuromodulatory drug Pifithrin-α. Together, these findings provide an essential foundation for the utilization of human brain organoids to study intact and disordered human brain network formation and illustrate their utility in therapeutic discovery.},
  author       = {Samarasinghe, Ranmal A. and Miranda, Osvaldo and Buth, Jessie E. and Mitchell, Simon and Ferando, Isabella and Watanabe, Momoko and Kurdian, Arinnae and Golshani, Peyman and Plath, Kathrin and Lowry, William E. and Parent, Jack M. and Mody, Istvan and Novitch, Bennett G.},
  issn         = {1546-1726},
  pages        = {32},
  publisher    = {Springer Nature},
  title        = {{Identification of neural oscillations and epileptiform changes in human brain organoids}},
  doi          = {10.1038/s41593-021-00906-5},
  volume       = {24},
  year         = {2021},
}

@unpublished{7358,
  abstract     = {Telencephalic organoids generated from human pluripotent stem cells (hPSCs) are emerging as an effective system to study the distinct features of the developing human brain and the underlying causes of many neurological disorders. While progress in organoid technology has been steadily advancing, many challenges remain including rampant batch-to-batch and cell line-to-cell line variability and irreproducibility. Here, we demonstrate that a major contributor to successful cortical organoid production is the manner in which hPSCs are maintained prior to differentiation. Optimal results were achieved using fibroblast-feeder-supported hPSCs compared to feeder-independent cells, related to differences in their transcriptomic states. Feeder-supported hPSCs display elevated activation of diverse TGFβ superfamily signaling pathways and increased expression of genes associated with naïve pluripotency. We further identify combinations of TGFβ-related growth factors that are necessary and together sufficient to impart broad telencephalic organoid competency to feeder-free hPSCs and enable reproducible formation of brain structures suitable for disease modeling.},
  author       = {Watanabe, Momoko and Haney, Jillian R. and Vishlaghi, Neda and Turcios, Felix and Buth, Jessie E. and Gu, Wen and Collier, Amanda J. and Miranda, Osvaldo and Chen, Di and Sabri, Shan and Clark, Amander T. and Plath, Kathrin and Christofk, Heather R. and Gandal, Michael J. and Novitch, Bennett G.},
  booktitle    = {bioRxiv},
  pages        = {75},
  publisher    = {Cold Spring Harbor Laboratory},
  title        = {{TGFβ superfamily signaling regulates the state of human stem cell pluripotency and competency to create telencephalic organoids}},
  doi          = {10.1101/2019.12.13.875773},
  year         = {2019},
}