Transcriptome Analysis of Small Molecule–Mediated Astrocyte-to-Neuron Reprogramming
Chemical reprogramming of astrocytes into neurons represents a promising approach to regenerate new neurons for brain repair, but the underlying mechanisms driving this trans-differentiation process are not well understood. We have recently identified four small molecules – CHIR99021, DAPT, LDN19318...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-05-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fcell.2019.00082/full |
| _version_ | 1819226309065179136 |
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| author | Ning-Xin Ma Jiu-Chao Yin Gong Chen |
| author_facet | Ning-Xin Ma Jiu-Chao Yin Gong Chen |
| author_sort | Ning-Xin Ma |
| collection | DOAJ |
| description | Chemical reprogramming of astrocytes into neurons represents a promising approach to regenerate new neurons for brain repair, but the underlying mechanisms driving this trans-differentiation process are not well understood. We have recently identified four small molecules – CHIR99021, DAPT, LDN193189, and SB431542 – that can efficiently reprogram cultured human fetal astrocytes into functional neurons. Here we employ the next generation of RNA-sequencing technology to investigate the transcriptome changes during the astrocyte-to-neuron (AtN) conversion process. We found that the four small molecules can rapidly activate the hedgehog signaling pathway while downregulating many glial genes such as FN1 and MYL9 within 24 h of treatment. Chemical reprogramming is mediated by several waves of differential gene expression, including upregulation of hedgehog, Wnt/β-catenin, and Notch signaling pathways, together with downregulation of TGF-β and JAK/STAT signaling pathways. Our gene network analyses reveal many well-connected hub genes such as repulsive guidance molecule A (RGMA), neuronatin (NNAT), neurogenin 2 (NEUROG2), NPTX2, MOXD1, JAG1, and GAP43, which may coordinate the chemical reprogramming process. Together, these findings provide critical insights into the molecular cascades triggered by a combination of small molecules that eventually leads to chemical conversion of astrocytes into neurons. |
| first_indexed | 2024-12-23T10:23:26Z |
| format | Article |
| id | doaj.art-aaa025f2284d4f2b8ad43f68bd165482 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-23T10:23:26Z |
| publishDate | 2019-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-aaa025f2284d4f2b8ad43f68bd1654822022-12-21T17:50:38ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2019-05-01710.3389/fcell.2019.00082453439Transcriptome Analysis of Small Molecule–Mediated Astrocyte-to-Neuron ReprogrammingNing-Xin MaJiu-Chao YinGong ChenChemical reprogramming of astrocytes into neurons represents a promising approach to regenerate new neurons for brain repair, but the underlying mechanisms driving this trans-differentiation process are not well understood. We have recently identified four small molecules – CHIR99021, DAPT, LDN193189, and SB431542 – that can efficiently reprogram cultured human fetal astrocytes into functional neurons. Here we employ the next generation of RNA-sequencing technology to investigate the transcriptome changes during the astrocyte-to-neuron (AtN) conversion process. We found that the four small molecules can rapidly activate the hedgehog signaling pathway while downregulating many glial genes such as FN1 and MYL9 within 24 h of treatment. Chemical reprogramming is mediated by several waves of differential gene expression, including upregulation of hedgehog, Wnt/β-catenin, and Notch signaling pathways, together with downregulation of TGF-β and JAK/STAT signaling pathways. Our gene network analyses reveal many well-connected hub genes such as repulsive guidance molecule A (RGMA), neuronatin (NNAT), neurogenin 2 (NEUROG2), NPTX2, MOXD1, JAG1, and GAP43, which may coordinate the chemical reprogramming process. Together, these findings provide critical insights into the molecular cascades triggered by a combination of small molecules that eventually leads to chemical conversion of astrocytes into neurons.https://www.frontiersin.org/article/10.3389/fcell.2019.00082/fullchemical reprogrammingtranscriptomeastrocyteneuronsignaling pathway |
| spellingShingle | Ning-Xin Ma Jiu-Chao Yin Gong Chen Transcriptome Analysis of Small Molecule–Mediated Astrocyte-to-Neuron Reprogramming Frontiers in Cell and Developmental Biology chemical reprogramming transcriptome astrocyte neuron signaling pathway |
| title | Transcriptome Analysis of Small Molecule–Mediated Astrocyte-to-Neuron Reprogramming |
| title_full | Transcriptome Analysis of Small Molecule–Mediated Astrocyte-to-Neuron Reprogramming |
| title_fullStr | Transcriptome Analysis of Small Molecule–Mediated Astrocyte-to-Neuron Reprogramming |
| title_full_unstemmed | Transcriptome Analysis of Small Molecule–Mediated Astrocyte-to-Neuron Reprogramming |
| title_short | Transcriptome Analysis of Small Molecule–Mediated Astrocyte-to-Neuron Reprogramming |
| title_sort | transcriptome analysis of small molecule mediated astrocyte to neuron reprogramming |
| topic | chemical reprogramming transcriptome astrocyte neuron signaling pathway |
| url | https://www.frontiersin.org/article/10.3389/fcell.2019.00082/full |
| work_keys_str_mv | AT ningxinma transcriptomeanalysisofsmallmoleculemediatedastrocytetoneuronreprogramming AT jiuchaoyin transcriptomeanalysisofsmallmoleculemediatedastrocytetoneuronreprogramming AT gongchen transcriptomeanalysisofsmallmoleculemediatedastrocytetoneuronreprogramming |