Unbiased identification of novel transcription factors in Striatal Compartmentation and Striosome maturation

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

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

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.

Original languageEnglish
Article numbere65979
JournaleLife
Volume10
DOIs
StatePublished - Oct 2021

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