Related Experiment Video
Updated: Dec 18, 2025
09:25
Lineage Tracing and Clonal Analysis in Developing Cerebral Cortex Using Mosaic Analysis with Double Markers MADM
Published on: May 8, 2020
11.2K
Parallel RNA and DNA analysis after deep sequencing (PRDD-seq) reveals cell type-specific lineage patterns in human
August Yue Huang1,2,3,4,5,6, Pengpeng Li1,2,3,4,5,6, Rachel E Rodin1,2,3,4,5,6,7,8
1Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA 02115.
Summary
Researchers developed parallel RNA and DNA analysis after deep sequencing (PRDD-seq) to map human brain cell development. This method reveals neuronal cell types, lineages, and birthdates, uncovering early precursor divergence and layered development.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Understanding human brain development requires elucidating cell lineage relationships.
- Single-cell and bulk DNA sequencing are crucial for analyzing cellular diversity.
Purpose of the Study:
- To develop a method for simultaneous reconstruction of neuronal cell type, lineage, and formation sequence.
- To analyze cell development in the postmortem human cerebral cortex.
Main Methods:
- Parallel RNA and DNA analysis after deep sequencing (PRDD-seq) was developed.
- PRDD-seq combines RNA analysis of neuronal cell types with DNA somatic mutations as lineage markers.
- Single-cell MosaicHunter (scMH) was used for joint analysis of single-cell and bulk DNA sequencing.
Main Results:
- PRDD-seq enabled simultaneous reconstruction of neuronal cell type, lineage, and birthdate in human brains.
- Analysis confirmed early divergence of excitatory and inhibitory neuron precursors.
- Established an "inside-out" layer formation for excitatory neurons and estimated ~10 excitatory neuron-restricted precursors per cortical column.
Conclusions:
- PRDD-seq provides quantitative details on mutation frequency and clonal patterns in human brain development.
- Revealed complex, subtype-specific neurogenesis patterns in inhibitory neurons, with conserved and primate-specific aspects.
- PRDD-seq is broadly applicable for single-cell resolution lineage and identity characterization in archival samples and various conditions.
