The coding and long noncoding single-cell atlas of the developing human fetal striatum

Area of Science:

• Neuroscience
• Developmental Biology
• Genomics

Background:

• Understanding human striatum development is crucial for neurological disease research.
• The transcriptional regulation of the developing striatum remains incompletely understood.

Purpose of the Study:

• To decode the transcriptional modules governing human striatum development.
• To identify novel long intergenic noncoding RNAs (lincRNAs) involved in striatal lineage commitment.

Main Methods:

• Profiling of 96,789 single cells from the early human fetal striatum.
• De novo identification and cataloging of 1116 long intergenic noncoding RNAs (lincRNAs).
• Uncovering and validating cell type-specific gene regulatory networks using in silico perturbation.

Main Results:

• D1 and D2 medium spiny neurons (MSNs) originate from a common progenitor.
• Lineage commitment occurs during the postmitotic transition via a pre-MSN phase.
• Human-specific lincRNAs were identified, contributing to the human-specific evolution of the striatum.

Conclusions:

• This study delineates the cellular hierarchies controlling MSN lineage commitment during human striatum development.
• Identified lincRNAs offer potential targets for understanding and treating striatal diseases.
• The findings provide insights into the molecular basis of human-specific brain evolution.