Unbiased identification of novel transcription factors in striatal compartmentation and striosome maturation.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34609283.
- Also identified by DOI 10.7554/eLife.65979 and PMC identifier 8492065.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 <i>Nr4a1</i>-EGFP striosome reporter mouse. Focusing on the striosome, we validated the localization and/or role of <i>Irx1</i>, <i>Foxf2</i>, <i>Olig2</i>, and <i>Stat1/2</i> in the developing striosome and the in vivo enhancer function of a striosome-specific open chromatin region 4.4 Kb downstream of <i>Olig2</i>. 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.
Medical subject headings
- Cell Differentiation
- Neostriatum
- Neurons
- Transcription Factors