Department of Biomedical Informatics and Medical Education, University of Washington, Seattle, United States
Jaroslav Bendl
Pamela 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
Pasha Apontes
Pamela 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
John Fullard
Pamela 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
Jordi Creus-Muncunill
Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, United States
Azadeh Reyahi
Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden
Ali M Nik
Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden
Peter Carlsson
Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden
Panos Roussos
Pamela 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 States
Sean D Mooney
Department of Biomedical Informatics and Medical Education, University of Washington, Seattle, United States
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.
