PUBLICATION
Whole-organism clone tracing using single-cell sequencing
- Authors
- Alemany, A., Florescu, M., Baron, C.S., Peterson-Maduro, J., van Oudenaarden, A.
- ID
- ZDB-PUB-180329-9
- Date
- 2018
- Source
- Nature 556(7699): 108-112 (Journal)
- Registered Authors
- Peterson-Maduroe, Josi
- Keywords
- none
- Datasets
- GEO:GSE102990
- MeSH Terms
-
- Animal Fins/cytology
- Animals
- Brain/cytology
- CRISPR-Cas Systems/genetics
- Cell Lineage*/genetics
- Cell Tracking/methods*
- Clone Cells/cytology*
- Clone Cells/metabolism*
- Embryonic Stem Cells/cytology
- Embryonic Stem Cells/metabolism
- Eye/cytology
- Female
- Genes, Reporter/genetics
- Hematopoietic Stem Cells/cytology
- Hematopoietic Stem Cells/metabolism
- Male
- Multipotent Stem Cells/cytology
- Multipotent Stem Cells/metabolism
- Organ Specificity
- Regeneration
- Sequence Analysis/methods*
- Single-Cell Analysis*
- Transcriptome
- Whole Body Imaging
- Zebrafish/anatomy & histology*
- Zebrafish/embryology
- Zebrafish/genetics
- PubMed
- 29590089 Full text @ Nature
Citation
Alemany, A., Florescu, M., Baron, C.S., Peterson-Maduro, J., van Oudenaarden, A. (2018) Whole-organism clone tracing using single-cell sequencing. Nature. 556(7699):108-112.
Abstract
Embryonic development is a crucial period in the life of a multicellular organism, during which limited sets of embryonic progenitors produce all cells in the adult body. Determining which fate these progenitors acquire in adult tissues requires the simultaneous measurement of clonal history and cell identity at single-cell resolution, which has been a major challenge. Clonal history has traditionally been investigated by microscopically tracking cells during development, monitoring the heritable expression of genetically encoded fluorescent proteins and, more recently, using next-generation sequencing technologies that exploit somatic mutations, microsatellite instability, transposon tagging, viral barcoding, CRISPR-Cas9 genome editing and Cre-loxP recombination. Single-cell transcriptomics provides a powerful platform for unbiased cell-type classification. Here we present ScarTrace, a single-cell sequencing strategy that enables the simultaneous quantification of clonal history and cell type for thousands of cells obtained from different organs of the adult zebrafish. Using ScarTrace, we show that a small set of multipotent embryonic progenitors generate all haematopoietic cells in the kidney marrow, and that many progenitors produce specific cell types in the eyes and brain. In addition, we study when embryonic progenitors commit to the left or right eye. ScarTrace reveals that epidermal and mesenchymal cells in the caudal fin arise from the same progenitors, and that osteoblast-restricted precursors can produce mesenchymal cells during regeneration. Furthermore, we identify resident immune cells in the fin with a distinct clonal origin from other blood cell types. We envision that similar approaches will have major applications in other experimental systems, in which the matching of embryonic clonal origin to adult cell type will ultimately allow reconstruction of how the adult body is built from a single cell.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping