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| Status |
Public on Jun 29, 2020 |
| Title |
Clonal relations in the mouse brain revealed by single-cell and spatial transcriptomics |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The mammalian brain contains many specialized cells that develop from a thin sheet of neuroepithelial progenitor cells. Single-cell transcriptomics revealed hundreds of molecularly diverse cell types in the nervous system, but the lineage relationships between mature cell types and progenitor cells are not well understood. Here we show in vivo barcoding of early progenitors to simultaneously profile cell phenotypes and clonal relations in the mouse brain using single-cell and spatial transcriptomics. By reconstructing thousands of clones, we discovered fate-restricted progenitor cells in the mouse hippocampal neuroepithelium and show that microglia are derived from few primitive myeloid precursors that massively expand to generate widely dispersed progeny. We combined spatial transcriptomics with clonal barcoding and disentangled migration patterns of clonally related cells in densely labelled tissue sections. Our approach enables high-throughput dense reconstruction of cell phenotypes and clonal relations at the single-cell and tissue level in individual animals and provides an integrated approach for understanding tissue architecture.
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| Overall design |
Lentiviral delivery of a transcribed barcode into neuroepithelial progenitor cells using in utero microinjection into the mouse forebrain at embryonic day 9.5 followed by RNA-seq analysis of barcoded cells at postnatal day 11-14.
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| Contributor(s) |
Ratz M, von Berlin L, Larsson L, Martin M, Westholm JO, La Manno G, Lundeberg J, Frisén J |
| Citation(s) |
35210624 |
| Submission date |
Jun 28, 2020 |
| Last update date |
Mar 31, 2022 |
| Contact name |
Michael Ratz |
| E-mail(s) |
michael.ratz@ki.se
|
| Organization name |
Karolinska Institute
|
| Department |
CMB
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| Lab |
Frisén
|
| Street address |
Solnavägen 9
|
| City |
Solna |
| ZIP/Postal code |
171 65 |
| Country |
Sweden |
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| Platforms (3) |
| GPL16417 |
Illumina MiSeq (Mus musculus) |
| GPL21626 |
NextSeq 550 (Mus musculus) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (37)
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| Relations |
| BioProject |
PRJNA642635 |
| SRA |
SRP269087 |
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