Rapid neurogenesis through transcriptional activation in human stem cells
Advances in cellular reprogramming and stem cell differentiation now enable ex vivo studies of human neuronal differentiation. However, it remains challenging to elucidate the underlying regulatory programs because differentiation protocols are laborious and often result in low neuron yields. Here,...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2014
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| Online Access: | http://hdl.handle.net/1721.1/92528 https://orcid.org/0000-0003-0396-2443 |
| _version_ | 1826205676349685760 |
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| author | Guye, Patrick Li, Yinqing Weiss, Ron Busskamp, Volker Lewis, Nathan E. Ng, Alex H. M. Shipman, Seth L. Byrne, Susan M. Li, Shangzhong Stadler, Michael Murn, Jernej Sanjana, Neville E Church, George M |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Guye, Patrick Li, Yinqing Weiss, Ron Busskamp, Volker Lewis, Nathan E. Ng, Alex H. M. Shipman, Seth L. Byrne, Susan M. Li, Shangzhong Stadler, Michael Murn, Jernej Sanjana, Neville E Church, George M |
| author_sort | Guye, Patrick |
| collection | MIT |
| description | Advances in cellular reprogramming and stem cell differentiation now enable ex vivo studies of human neuronal differentiation. However, it remains challenging to elucidate the underlying regulatory programs because differentiation protocols are laborious and often result in low neuron yields. Here, we overexpressed two Neurogenin transcription factors in human‐induced pluripotent stem cells and obtained neurons with bipolar morphology in 4 days, at greater than 90% purity. The high purity enabled mRNA and microRNA expression profiling during neurogenesis, thus revealing the genetic programs involved in the rapid transition from stem cell to neuron. The resulting cells exhibited transcriptional, morphological and functional signatures of differentiated neurons, with greatest transcriptional similarity to prenatal human brain samples. Our analysis revealed a network of key transcription factors and microRNAs that promoted loss of pluripotency and rapid neurogenesis via progenitor states. Perturbations of key transcription factors affected homogeneity and phenotypic properties of the resulting neurons, suggesting that a systems‐level view of the molecular biology of differentiation may guide subsequent manipulation of human stem cells to rapidly obtain diverse neuronal types. |
| first_indexed | 2024-09-23T13:16:51Z |
| format | Article |
| id | mit-1721.1/92528 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:16:51Z |
| publishDate | 2014 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/925282022-09-28T13:06:27Z Rapid neurogenesis through transcriptional activation in human stem cells Guye, Patrick Li, Yinqing Weiss, Ron Busskamp, Volker Lewis, Nathan E. Ng, Alex H. M. Shipman, Seth L. Byrne, Susan M. Li, Shangzhong Stadler, Michael Murn, Jernej Sanjana, Neville E Church, George M Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science McGovern Institute for Brain Research at MIT Picower Institute for Learning and Memory Program in Media Arts and Sciences (Massachusetts Institute of Technology) Guye, Patrick Li, Yinqing Weiss, Ron Sanjana, Neville Murn, Jernej Church, George M. Advances in cellular reprogramming and stem cell differentiation now enable ex vivo studies of human neuronal differentiation. However, it remains challenging to elucidate the underlying regulatory programs because differentiation protocols are laborious and often result in low neuron yields. Here, we overexpressed two Neurogenin transcription factors in human‐induced pluripotent stem cells and obtained neurons with bipolar morphology in 4 days, at greater than 90% purity. The high purity enabled mRNA and microRNA expression profiling during neurogenesis, thus revealing the genetic programs involved in the rapid transition from stem cell to neuron. The resulting cells exhibited transcriptional, morphological and functional signatures of differentiated neurons, with greatest transcriptional similarity to prenatal human brain samples. Our analysis revealed a network of key transcription factors and microRNAs that promoted loss of pluripotency and rapid neurogenesis via progenitor states. Perturbations of key transcription factors affected homogeneity and phenotypic properties of the resulting neurons, suggesting that a systems‐level view of the molecular biology of differentiation may guide subsequent manipulation of human stem cells to rapidly obtain diverse neuronal types. National Institutes of Health (U.S.) (Grant P50 HG005550) Merkin, Richard N. National Science Foundation (U.S.). Emergent Behaviors of Integrated Cellular Systems (Grant 0939511) Synthetic Biology Engineering Research Center (Grant 0540879) Swiss National Science Foundation Ernst Schering Research Foundation 2014-12-29T18:18:37Z 2014-12-29T18:18:37Z 2014-11 Article http://purl.org/eprint/type/JournalArticle 1744-4292 http://hdl.handle.net/1721.1/92528 Busskamp, Volker, Nathan E. Lewis, Patrick Guye, Alex H.M. Ng, Seth L. Shipman, Susan M. Byrne, Neville E. Sanjana, et al. “Rapid Neurogenesis through Transcriptional Activation in Human Stem Cells.” Molecular Systems Biology 10, no. 11 (November 1, 2014): 760–760. https://orcid.org/0000-0003-0396-2443 en_US http://dx.doi.org/10.15252/msb.20145508 Molecular Systems Biology Creative Commons Attribution http://creativecommons.org/licenses/by/4.0/ application/pdf Nature Publishing Group EMBO Press |
| spellingShingle | Guye, Patrick Li, Yinqing Weiss, Ron Busskamp, Volker Lewis, Nathan E. Ng, Alex H. M. Shipman, Seth L. Byrne, Susan M. Li, Shangzhong Stadler, Michael Murn, Jernej Sanjana, Neville E Church, George M Rapid neurogenesis through transcriptional activation in human stem cells |
| title | Rapid neurogenesis through transcriptional activation in human stem cells |
| title_full | Rapid neurogenesis through transcriptional activation in human stem cells |
| title_fullStr | Rapid neurogenesis through transcriptional activation in human stem cells |
| title_full_unstemmed | Rapid neurogenesis through transcriptional activation in human stem cells |
| title_short | Rapid neurogenesis through transcriptional activation in human stem cells |
| title_sort | rapid neurogenesis through transcriptional activation in human stem cells |
| url | http://hdl.handle.net/1721.1/92528 https://orcid.org/0000-0003-0396-2443 |
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