TGFβ superfamily signaling regulates the state of human stem cell pluripotency and competency to create telencephalic organoids

M. Watanabe, J.R. Haney, N. Vishlaghi, F. Turcios, J.E. Buth, W. Gu, A.J. Collier, O. Miranda, D. Chen, S. Sabri, A.T. Clark, K. Plath, H.R. Christofk, M.J. Gandal, B.G. Novitch, BioRxiv (2019).

Preprint | Published | English
Author
Watanabe, Momoko; Haney, Jillian R.; Vishlaghi, Neda; Turcios, Felix; Buth, Jessie E.; Gu, Wen; Collier, Amanda J.; Miranda, OsvaldoIST Austria ; Chen, Di; Sabri, Shan; Clark, Amander T.; Plath, Kathrin
All
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.
Publishing Year
Date Published
2019-12-13
Journal Title
bioRxiv
Page
75
IST-REx-ID

Cite this

Watanabe M, Haney JR, Vishlaghi N, et al. TGFβ superfamily signaling regulates the state of human stem cell pluripotency and competency to create telencephalic organoids. bioRxiv. 2019.
Watanabe, M., Haney, J. R., Vishlaghi, N., Turcios, F., Buth, J. E., Gu, W., … Novitch, B. G. (2019). TGFβ superfamily signaling regulates the state of human stem cell pluripotency and competency to create telencephalic organoids. BioRxiv. Cold Spring Harbor Laboratory.
Watanabe, Momoko, Jillian R. Haney, Neda Vishlaghi, Felix Turcios, Jessie E. Buth, Wen Gu, Amanda J. Collier, et al. “TGFβ Superfamily Signaling Regulates the State of Human Stem Cell Pluripotency and Competency to Create Telencephalic Organoids.” BioRxiv. Cold Spring Harbor Laboratory, 2019.
M. Watanabe et al., “TGFβ superfamily signaling regulates the state of human stem cell pluripotency and competency to create telencephalic organoids,” bioRxiv. Cold Spring Harbor Laboratory, 2019.
Watanabe M, Haney JR, Vishlaghi N, Turcios F, Buth JE, Gu W, Collier AJ, Miranda O, Chen D, Sabri S, Clark AT, Plath K, Christofk HR, Gandal MJ, Novitch BG. 2019. TGFβ superfamily signaling regulates the state of human stem cell pluripotency and competency to create telencephalic organoids. bioRxiv.
Watanabe, Momoko, et al. “TGFβ Superfamily Signaling Regulates the State of Human Stem Cell Pluripotency and Competency to Create Telencephalic Organoids.” BioRxiv, Cold Spring Harbor Laboratory, 2019.
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