The striatum contributes to many cognitive processes and disorders, but its cell types are incompletely characterized. We show that microfluidic and FACS-based single-cell RNA sequencing of mouse striatum provides a well-resolved classification of striatal cell type diversity. Transcriptome analysis revealed ten differentiated, distinct cell types, including neurons, astrocytes, oligodendrocytes, ependymal, immune, and vascular cells, and enabled the discovery of numerous marker genes. Furthermore, we identified two discrete subtypes of medium spiny neurons (MSNs) that have specific markers and that overexpress genes linked to cognitive disorders and addiction. We also describe continuous cellular identities, which increase heterogeneity within discrete cell types. Finally, we identified cell type-specific transcription and splicing factors that shape cellular identities by regulating splicing and expression patterns. Our findings suggest that functional diversity within a complex tissue arises from a small number of discrete cell types, which can exist in a continuous spectrum of functional states.
Bibliographical noteFunding Information:
We would like to thank all members of the S.R.Q. and T.C.S. laboratories for helpful discussions and Ben Barres for providing Aldh1l1-GFP mice. This work was supported by grants from the NIDA (K99DA038112 to O.G.), the NIH (R37MH52804 to T.C.S.), and the Brain and Behavior Research Foundation (to O.G.). Authors disclose the following: Stephen R. Quake is a founder, consultant, and shareholder of Fluidigm Corporation.
© 2016 The Authors