Induction of human somatostatin and parvalbumin neurons by expressing a single transcription factor LIM homeobox 6
Human GABAergic interneurons (GIN) are implicated in normal brain function and in numerous mental disorders. However, the generation of functional human GIN subtypes from human pluripotent stem cells (hPSCs) has not been established. By expressing LHX6, a transcriptional factor that is critical for...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2018-09-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/37382 |
| _version_ | 1811253184570589184 |
|---|---|
| author | Fang Yuan Xin Chen Kai-Heng Fang Yuanyuan Wang Mingyan Lin Shi-Bo Xu Hai-Qin Huo Min Xu Lixiang Ma Yuejun Chen Shuijin He Yan Liu |
| author_facet | Fang Yuan Xin Chen Kai-Heng Fang Yuanyuan Wang Mingyan Lin Shi-Bo Xu Hai-Qin Huo Min Xu Lixiang Ma Yuejun Chen Shuijin He Yan Liu |
| author_sort | Fang Yuan |
| collection | DOAJ |
| description | Human GABAergic interneurons (GIN) are implicated in normal brain function and in numerous mental disorders. However, the generation of functional human GIN subtypes from human pluripotent stem cells (hPSCs) has not been established. By expressing LHX6, a transcriptional factor that is critical for GIN development, we induced hPSCs to form GINs, including somatostatin (SST, 29%) and parvalbumin (PV, 21%) neurons. Our RNAseq results also confirmed the alteration of GIN identity with the overexpression of LHX6. Five months after transplantation into the mouse brain, the human GABA precursors generated increased population of SST and PV neurons by overexpressing LHX6. Importantly, the grafted human GINs exhibited functional electrophysiological properties and even fast-spiking-like action potentials. Thus, expression of the single transcription factor LHX6 under our GIN differentiation condition is sufficient to robustly induce human PV and SST subtypes. |
| first_indexed | 2024-04-12T16:47:08Z |
| format | Article |
| id | doaj.art-76006e8c49c0472ea3a2caf0ff4e71f1 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:47:08Z |
| publishDate | 2018-09-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-76006e8c49c0472ea3a2caf0ff4e71f12022-12-22T03:24:32ZengeLife Sciences Publications LtdeLife2050-084X2018-09-01710.7554/eLife.37382Induction of human somatostatin and parvalbumin neurons by expressing a single transcription factor LIM homeobox 6Fang Yuan0Xin Chen1Kai-Heng Fang2Yuanyuan Wang3Mingyan Lin4Shi-Bo Xu5Hai-Qin Huo6Min Xu7Lixiang Ma8Yuejun Chen9Shuijin He10Yan Liu11https://orcid.org/0000-0003-2918-5398Institute for Stem Cell and Neural Regeneration, School of Pharmacy, Nanjing Medical University, Nanjing, China; State Key Laboratory of Reproductive Medicine, Nanjing Medical Unveristy, Nanjing, ChinaSchool of Life Science and Technology, ShanghaiTech University, Shanghai, ChinaInstitute for Stem Cell and Neural Regeneration, School of Pharmacy, Nanjing Medical University, Nanjing, ChinaDepartment of Neuroscience, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, ChinaDepartment of Neuroscience, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, ChinaInstitute for Stem Cell and Neural Regeneration, School of Pharmacy, Nanjing Medical University, Nanjing, ChinaInstitute for Stem Cell and Neural Regeneration, School of Pharmacy, Nanjing Medical University, Nanjing, ChinaInstitute for Stem Cell and Neural Regeneration, School of Pharmacy, Nanjing Medical University, Nanjing, ChinaDepartment of Human Anatomy and Histology, Institute of Stem Cells and Regenerative Medicine, Fudan University Shanghai Medical School, Shanghai, ChinaInstitute of Neuroscience, Chinese Academy of Sciences, Beijing, ChinaSchool of Life Science and Technology, ShanghaiTech University, Shanghai, ChinaInstitute for Stem Cell and Neural Regeneration, School of Pharmacy, Nanjing Medical University, Nanjing, China; State Key Laboratory of Reproductive Medicine, Nanjing Medical Unveristy, Nanjing, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, ChinaHuman GABAergic interneurons (GIN) are implicated in normal brain function and in numerous mental disorders. However, the generation of functional human GIN subtypes from human pluripotent stem cells (hPSCs) has not been established. By expressing LHX6, a transcriptional factor that is critical for GIN development, we induced hPSCs to form GINs, including somatostatin (SST, 29%) and parvalbumin (PV, 21%) neurons. Our RNAseq results also confirmed the alteration of GIN identity with the overexpression of LHX6. Five months after transplantation into the mouse brain, the human GABA precursors generated increased population of SST and PV neurons by overexpressing LHX6. Importantly, the grafted human GINs exhibited functional electrophysiological properties and even fast-spiking-like action potentials. Thus, expression of the single transcription factor LHX6 under our GIN differentiation condition is sufficient to robustly induce human PV and SST subtypes.https://elifesciences.org/articles/37382direct differentiationPV neuronSST neuronHiPSCs |
| spellingShingle | Fang Yuan Xin Chen Kai-Heng Fang Yuanyuan Wang Mingyan Lin Shi-Bo Xu Hai-Qin Huo Min Xu Lixiang Ma Yuejun Chen Shuijin He Yan Liu Induction of human somatostatin and parvalbumin neurons by expressing a single transcription factor LIM homeobox 6 eLife direct differentiation PV neuron SST neuron HiPSCs |
| title | Induction of human somatostatin and parvalbumin neurons by expressing a single transcription factor LIM homeobox 6 |
| title_full | Induction of human somatostatin and parvalbumin neurons by expressing a single transcription factor LIM homeobox 6 |
| title_fullStr | Induction of human somatostatin and parvalbumin neurons by expressing a single transcription factor LIM homeobox 6 |
| title_full_unstemmed | Induction of human somatostatin and parvalbumin neurons by expressing a single transcription factor LIM homeobox 6 |
| title_short | Induction of human somatostatin and parvalbumin neurons by expressing a single transcription factor LIM homeobox 6 |
| title_sort | induction of human somatostatin and parvalbumin neurons by expressing a single transcription factor lim homeobox 6 |
| topic | direct differentiation PV neuron SST neuron HiPSCs |
| url | https://elifesciences.org/articles/37382 |
| work_keys_str_mv | AT fangyuan inductionofhumansomatostatinandparvalbuminneuronsbyexpressingasingletranscriptionfactorlimhomeobox6 AT xinchen inductionofhumansomatostatinandparvalbuminneuronsbyexpressingasingletranscriptionfactorlimhomeobox6 AT kaihengfang inductionofhumansomatostatinandparvalbuminneuronsbyexpressingasingletranscriptionfactorlimhomeobox6 AT yuanyuanwang inductionofhumansomatostatinandparvalbuminneuronsbyexpressingasingletranscriptionfactorlimhomeobox6 AT mingyanlin inductionofhumansomatostatinandparvalbuminneuronsbyexpressingasingletranscriptionfactorlimhomeobox6 AT shiboxu inductionofhumansomatostatinandparvalbuminneuronsbyexpressingasingletranscriptionfactorlimhomeobox6 AT haiqinhuo inductionofhumansomatostatinandparvalbuminneuronsbyexpressingasingletranscriptionfactorlimhomeobox6 AT minxu inductionofhumansomatostatinandparvalbuminneuronsbyexpressingasingletranscriptionfactorlimhomeobox6 AT lixiangma inductionofhumansomatostatinandparvalbuminneuronsbyexpressingasingletranscriptionfactorlimhomeobox6 AT yuejunchen inductionofhumansomatostatinandparvalbuminneuronsbyexpressingasingletranscriptionfactorlimhomeobox6 AT shuijinhe inductionofhumansomatostatinandparvalbuminneuronsbyexpressingasingletranscriptionfactorlimhomeobox6 AT yanliu inductionofhumansomatostatinandparvalbuminneuronsbyexpressingasingletranscriptionfactorlimhomeobox6 |