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TGFβ superfamily signaling regulates the state of human stem cell pluripotency and capacity to create well-structured telencephalic organoids
Telencephalic organoids generated from human pluripotent stem cells (hPSCs) are a promising system for studying the distinct features of the developing human brain and the underlying causes of many neurological disorders. While organoid technology is steadily advancing, many challenges remain, inclu...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9561534/ https://www.ncbi.nlm.nih.gov/pubmed/36179695 http://dx.doi.org/10.1016/j.stemcr.2022.08.013 |
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author | Watanabe, Momoko Buth, Jessie E. Haney, Jillian R. Vishlaghi, Neda Turcios, Felix Elahi, Lubayna S. Gu, Wen Pearson, Caroline A. Kurdian, Arinnae Baliaouri, Natella V. Collier, Amanda J. Miranda, Osvaldo A. Dunn, Natassia Chen, Di Sabri, Shan Torre-Ubieta, Luis de la Clark, Amander T. Plath, Kathrin Christofk, Heather R. Kornblum, Harley I. Gandal, Michael J. Novitch, Bennett G. |
author_facet | Watanabe, Momoko Buth, Jessie E. Haney, Jillian R. Vishlaghi, Neda Turcios, Felix Elahi, Lubayna S. Gu, Wen Pearson, Caroline A. Kurdian, Arinnae Baliaouri, Natella V. Collier, Amanda J. Miranda, Osvaldo A. Dunn, Natassia Chen, Di Sabri, Shan Torre-Ubieta, Luis de la Clark, Amander T. Plath, Kathrin Christofk, Heather R. Kornblum, Harley I. Gandal, Michael J. Novitch, Bennett G. |
author_sort | Watanabe, Momoko |
collection | PubMed |
description | Telencephalic organoids generated from human pluripotent stem cells (hPSCs) are a promising system for studying the distinct features of the developing human brain and the underlying causes of many neurological disorders. While organoid technology is steadily advancing, many challenges remain, including potential batch-to-batch and cell-line-to-cell-line variability, and structural inconsistency. Here, we demonstrate that a major contributor to cortical organoid quality is the way hPSCs are maintained prior to differentiation. Optimal results were achieved using particular fibroblast-feeder-supported hPSCs rather than feeder-independent cells, differences that were reflected in their transcriptomic states at the outset. Feeder-supported hPSCs displayed activation of diverse transforming growth factor β (TGFβ) superfamily signaling pathways and increased expression of genes connected to naive pluripotency. We further identified combinations of TGFβ-related growth factors that are necessary and together sufficient to impart broad telencephalic organoid competency to feeder-free hPSCs and enhance the formation of well-structured brain tissues suitable for disease modeling. |
format | Online Article Text |
id | pubmed-9561534 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-95615342022-10-15 TGFβ superfamily signaling regulates the state of human stem cell pluripotency and capacity to create well-structured telencephalic organoids Watanabe, Momoko Buth, Jessie E. Haney, Jillian R. Vishlaghi, Neda Turcios, Felix Elahi, Lubayna S. Gu, Wen Pearson, Caroline A. Kurdian, Arinnae Baliaouri, Natella V. Collier, Amanda J. Miranda, Osvaldo A. Dunn, Natassia Chen, Di Sabri, Shan Torre-Ubieta, Luis de la Clark, Amander T. Plath, Kathrin Christofk, Heather R. Kornblum, Harley I. Gandal, Michael J. Novitch, Bennett G. Stem Cell Reports Article Telencephalic organoids generated from human pluripotent stem cells (hPSCs) are a promising system for studying the distinct features of the developing human brain and the underlying causes of many neurological disorders. While organoid technology is steadily advancing, many challenges remain, including potential batch-to-batch and cell-line-to-cell-line variability, and structural inconsistency. Here, we demonstrate that a major contributor to cortical organoid quality is the way hPSCs are maintained prior to differentiation. Optimal results were achieved using particular fibroblast-feeder-supported hPSCs rather than feeder-independent cells, differences that were reflected in their transcriptomic states at the outset. Feeder-supported hPSCs displayed activation of diverse transforming growth factor β (TGFβ) superfamily signaling pathways and increased expression of genes connected to naive pluripotency. We further identified combinations of TGFβ-related growth factors that are necessary and together sufficient to impart broad telencephalic organoid competency to feeder-free hPSCs and enhance the formation of well-structured brain tissues suitable for disease modeling. Elsevier 2022-09-29 /pmc/articles/PMC9561534/ /pubmed/36179695 http://dx.doi.org/10.1016/j.stemcr.2022.08.013 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Watanabe, Momoko Buth, Jessie E. Haney, Jillian R. Vishlaghi, Neda Turcios, Felix Elahi, Lubayna S. Gu, Wen Pearson, Caroline A. Kurdian, Arinnae Baliaouri, Natella V. Collier, Amanda J. Miranda, Osvaldo A. Dunn, Natassia Chen, Di Sabri, Shan Torre-Ubieta, Luis de la Clark, Amander T. Plath, Kathrin Christofk, Heather R. Kornblum, Harley I. Gandal, Michael J. Novitch, Bennett G. TGFβ superfamily signaling regulates the state of human stem cell pluripotency and capacity to create well-structured telencephalic organoids |
title | TGFβ superfamily signaling regulates the state of human stem cell pluripotency and capacity to create well-structured telencephalic organoids |
title_full | TGFβ superfamily signaling regulates the state of human stem cell pluripotency and capacity to create well-structured telencephalic organoids |
title_fullStr | TGFβ superfamily signaling regulates the state of human stem cell pluripotency and capacity to create well-structured telencephalic organoids |
title_full_unstemmed | TGFβ superfamily signaling regulates the state of human stem cell pluripotency and capacity to create well-structured telencephalic organoids |
title_short | TGFβ superfamily signaling regulates the state of human stem cell pluripotency and capacity to create well-structured telencephalic organoids |
title_sort | tgfβ superfamily signaling regulates the state of human stem cell pluripotency and capacity to create well-structured telencephalic organoids |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9561534/ https://www.ncbi.nlm.nih.gov/pubmed/36179695 http://dx.doi.org/10.1016/j.stemcr.2022.08.013 |
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