Unbiased identification of novel transcription factors in striatal compartmentation and striosome maturation
Many diseases are linked to dysregulation of the striatum. Striatal function depends on neuronal compartmentation into striosomes and matrix. Striatal projection neurons are GABAergic medium spiny neurons (MSNs), subtyped by selective expression of receptors, neuropeptides, and other gene families....
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2021-10-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/65979 |
| _version_ | 1811180398093271040 |
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| author | Maria-Daniela Cirnaru Sicheng Song Kizito-Tshitoko Tshilenge Chuhyon Corwin Justyna Mleczko Carlos Galicia Aguirre Houda Benlhabib Jaroslav Bendl Pasha Apontes John Fullard Jordi Creus-Muncunill Azadeh Reyahi Ali M Nik Peter Carlsson Panos Roussos Sean D Mooney Lisa M Ellerby Michelle E Ehrlich |
| author_facet | Maria-Daniela Cirnaru Sicheng Song Kizito-Tshitoko Tshilenge Chuhyon Corwin Justyna Mleczko Carlos Galicia Aguirre Houda Benlhabib Jaroslav Bendl Pasha Apontes John Fullard Jordi Creus-Muncunill Azadeh Reyahi Ali M Nik Peter Carlsson Panos Roussos Sean D Mooney Lisa M Ellerby Michelle E Ehrlich |
| author_sort | Maria-Daniela Cirnaru |
| collection | DOAJ |
| description | Many diseases are linked to dysregulation of the striatum. Striatal function depends on neuronal compartmentation into striosomes and matrix. Striatal projection neurons are GABAergic medium spiny neurons (MSNs), subtyped by selective expression of receptors, neuropeptides, and other gene families. Neurogenesis of the striosome and matrix occurs in separate waves, but the factors regulating compartmentation and neuronal differentiation are largely unidentified. We performed RNA- and ATAC-seq on sorted striosome and matrix cells at postnatal day 3, using the Nr4a1-EGFP striosome reporter mouse. Focusing on the striosome, we validated the localization and/or role of Irx1, Foxf2, Olig2, and Stat1/2 in the developing striosome and the in vivo enhancer function of a striosome-specific open chromatin region 4.4 Kb downstream of Olig2. These data provide novel tools to dissect and manipulate the networks regulating MSN compartmentation and differentiation, including in human iPSC-derived striatal neurons for disease modeling and drug discovery. |
| first_indexed | 2024-04-11T09:01:28Z |
| format | Article |
| id | doaj.art-301679f6c49048c8a4afba920502c74a |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:01:28Z |
| publishDate | 2021-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-301679f6c49048c8a4afba920502c74a2022-12-22T04:32:45ZengeLife Sciences Publications LtdeLife2050-084X2021-10-011010.7554/eLife.65979Unbiased identification of novel transcription factors in striatal compartmentation and striosome maturationMaria-Daniela Cirnaru0Sicheng Song1Kizito-Tshitoko Tshilenge2Chuhyon Corwin3Justyna Mleczko4Carlos Galicia Aguirre5Houda Benlhabib6https://orcid.org/0000-0002-7776-1508Jaroslav Bendl7Pasha Apontes8John Fullard9Jordi Creus-Muncunill10Azadeh Reyahi11Ali M Nik12Peter Carlsson13Panos Roussos14Sean D Mooney15Lisa M Ellerby16https://orcid.org/0000-0002-9050-7977Michelle E Ehrlich17https://orcid.org/0000-0001-9397-686XDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, United StatesDepartment of Biomedical Informatics and Medical Education, University of Washington, Seattle, United StatesBuck Institute for Research on Aging, Novato, United StatesDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, United StatesDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, United StatesBuck Institute for Research on Aging, Novato, United StatesDepartment of Biomedical Informatics and Medical Education, University of Washington, Seattle, United StatesPamela Sklar Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, United States; Institute for Genomics and Multiscale Biology, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, United States; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, United StatesPamela Sklar Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, United States; Institute for Genomics and Multiscale Biology, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, United States; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, United StatesPamela Sklar Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, United States; Institute for Genomics and Multiscale Biology, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, United States; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, United StatesDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, United StatesDepartment of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, SwedenDepartment of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, SwedenDepartment of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, SwedenPamela Sklar Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, United States; Institute for Genomics and Multiscale Biology, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, United States; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, United States; Mental Illness Research, Education, and Clinical Center (VISN 2 South), Bronx, United StatesDepartment of Biomedical Informatics and Medical Education, University of Washington, Seattle, United StatesBuck Institute for Research on Aging, Novato, United StatesDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, United StatesMany diseases are linked to dysregulation of the striatum. Striatal function depends on neuronal compartmentation into striosomes and matrix. Striatal projection neurons are GABAergic medium spiny neurons (MSNs), subtyped by selective expression of receptors, neuropeptides, and other gene families. Neurogenesis of the striosome and matrix occurs in separate waves, but the factors regulating compartmentation and neuronal differentiation are largely unidentified. We performed RNA- and ATAC-seq on sorted striosome and matrix cells at postnatal day 3, using the Nr4a1-EGFP striosome reporter mouse. Focusing on the striosome, we validated the localization and/or role of Irx1, Foxf2, Olig2, and Stat1/2 in the developing striosome and the in vivo enhancer function of a striosome-specific open chromatin region 4.4 Kb downstream of Olig2. These data provide novel tools to dissect and manipulate the networks regulating MSN compartmentation and differentiation, including in human iPSC-derived striatal neurons for disease modeling and drug discovery.https://elifesciences.org/articles/65979StriosomeOlig2striatumNr4a1Foxf2transcription factors |
| spellingShingle | Maria-Daniela Cirnaru Sicheng Song Kizito-Tshitoko Tshilenge Chuhyon Corwin Justyna Mleczko Carlos Galicia Aguirre Houda Benlhabib Jaroslav Bendl Pasha Apontes John Fullard Jordi Creus-Muncunill Azadeh Reyahi Ali M Nik Peter Carlsson Panos Roussos Sean D Mooney Lisa M Ellerby Michelle E Ehrlich Unbiased identification of novel transcription factors in striatal compartmentation and striosome maturation eLife Striosome Olig2 striatum Nr4a1 Foxf2 transcription factors |
| title | Unbiased identification of novel transcription factors in striatal compartmentation and striosome maturation |
| title_full | Unbiased identification of novel transcription factors in striatal compartmentation and striosome maturation |
| title_fullStr | Unbiased identification of novel transcription factors in striatal compartmentation and striosome maturation |
| title_full_unstemmed | Unbiased identification of novel transcription factors in striatal compartmentation and striosome maturation |
| title_short | Unbiased identification of novel transcription factors in striatal compartmentation and striosome maturation |
| title_sort | unbiased identification of novel transcription factors in striatal compartmentation and striosome maturation |
| topic | Striosome Olig2 striatum Nr4a1 Foxf2 transcription factors |
| url | https://elifesciences.org/articles/65979 |
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