Early developmental asymmetries in cell lineage trees in living individuals

Science. 2021 Mar 19;371(6535):1245-1248. doi: 10.1126/science.abe0981.

Abstract

Mosaic mutations can be used to track cell lineages in humans. We used cell cloning to analyze embryonic cell lineages in two living individuals and a postmortem human specimen. Of 10 reconstructed postzygotic divisions, none resulted in balanced contributions of daughter lineages to tissues. In both living individuals, one of two lineages from the first cleavage was dominant across tissues, with 90% frequency in blood. We propose that the efficiency of DNA repair contributes to lineage imbalance. Allocation of lineages in postmortem brain correlated with anterior-posterior axis, associating lineage history with cell fate choices in embryos. We establish a minimally invasive framework for defining cell lineages in any living individual, which paves the way for studying their relevance in health and disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Blastocyst / cytology
  • Blastomeres / cytology*
  • Blood Cells
  • Cell Differentiation
  • Cell Division*
  • Cell Line
  • Cell Lineage*
  • DNA Repair
  • Embryonic Development*
  • Female
  • Fetus / cytology
  • Genetic Variation
  • Genome, Human
  • Humans
  • INDEL Mutation
  • Induced Pluripotent Stem Cells / cytology
  • Male
  • Neural Stem Cells / cytology
  • Polymorphism, Single Nucleotide