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Cited by 127Single-cell and spatial transcriptomicsNeurogenesis and neuroplasticity mechanismsDevelopmental Biology and Gene Regulation

Clonal relations in the mouse brain revealed by single-cell and spatial transcriptomics

Open access
Ratz, Michael, von Berlin, Leonie, Larsson, Ludvig, Martin, Marcel, Westholm, Jakub Orzechowski, La Manno, Gioele, Lundeberg, Joakim, Frisén, Jonas·2022·Nature Neuroscience
DOI 10.1038/s41593-022-01011-xPMC PMC8904259
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Abstract

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 labeled 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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  • YS-derived microglia persist throughout adulthood and display proliferation and self-renewal potential.

    “YS-derived microglia persist throughout adulthood displaying considerable proliferation and self-renewal potential 4,5 .”

    From Clonal hematopoiesis-associated motoric deficits caused by monocyte-derived microglia accumulating in aging mice (2025) · cites this paper as [5]

    The Main section reports that microglia arise from a limited number of progenitors that undergo massive clonal expansion, and the Results describe their early embryonic origins. The Discussion links large clone sizes to proliferation during CNS colonization, but it does not establish that yolk-sac-derived microglia self-renew or retain considerable proliferative potential throughout adulthood. No page numbers are available in our copy. (LLM, conf=0.84)

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References 62 · Cited by 127

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Authors
Ratz, M., von Berlin, L., Larsson, L., Martin, M., Westholm, J. O., La Manno, G., Lundeberg, J., & Frisén, J.
Affiliations
  • Karolinska Institutet (SE)
  • Science for Life Laboratory (SE)
  • Stockholm University (SE)
Corresponding author
Frisén, Jonas
ORCID
Venue
Nature Neuroscience
Publisher
Springer Science and Business Media LLC
Published
2022-02-24
Volume
25
Issue
3
Pages
285-294
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
DOI
10.1038/s41593-022-01011-x
PMC
PMC8904259
OpenAlex
W4213458181
Cited by
127
References
62
Citations by year
2026: 26 · 2025: 35 · 2024: 24 · 2023: 28 · 2022: 14
FWCI
8.49
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
Funders
  • Deutsche Forschungsgemeinschaft
  • Stiftelsen för Strategisk Forskning (SB16-0014)
  • Cancerfonden
  • Karolinska Institutet
  • Knut och Alice Wallenbergs Stiftelse (2018.0063)
  • Vetenskapsrådet (D0761801)
  • Science for Life Laboratory
  • Uppsala Multidisciplinary Center for Advanced Computational Science
  • H2020 European Research Council (695096)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
microglial origin, myeloid precursors, cell lineage, cell migration, cell fate restriction, mouse brain, single-cell transcriptomics, spatial transcriptomics, tissue structure
MeSH terms
Animals, Brain, Cell Differentiation, Clone Cells, Mammals, Stem Cells, Neuroepithelial Cells, Mice, Transcriptome

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