SUPR
Next-generation lineage and circuit tracing of the nervous system
Dnr:

NAISS 2024/22-52

Type:

NAISS Small Compute

Principal Investigator:

Michael Ratz

Affiliation:

Karolinska Institutet

Start Date:

2024-02-01

End Date:

2025-02-01

Primary Classification:

10614: Developmental Biology

Allocation

Abstract

Lineage tracing is an important method for the identification of all progeny originating from a single cell. This is particularly interesting for complex tissues like the brain derived from a small number of homogenous neural stem cells that diversify into hundreds to thousands of distinct cell types. While lineage tracing is widely used to study multicellular systems, it scales poorly to whole, complex tissues and organisms. The overall aim of this project is to use a large number (thousands to millions) of unique genetic barcodes to track the developmental origins of the mammalian brain during normal development and in mouse models of autism. We will use single-cell and spatial transcriptomics to read out barcodes and reconstruct lineages using computational approaches. Neural circuit tracing is a critical method to reveal synaptic networks in the nervous system. Similarly to lineage tracing, current approaches in circuit tracing scale poorly to large brains. In this part of the project, we will use barcoded rabies virus to reveal 100s-1000s of synaptic networks simultaneously in the same brain together with gene expression information. We will use single and spatial transcriptomics to read out barcodes and focus on the development of synaptic networks during early postnatal stages of the mouse brain in health and disease.