Landmarks of human embryonic development inscribed in somatic mutations

Area of Science:

• Developmental Biology
• Genomics
• Human Embryogenesis

Background:

• Understanding human embryonic development is crucial but lacks direct lineage information.
• Somatic mutations accumulate during development and can serve as lineage markers.

Purpose of the Study:

• To reconstruct early human embryonic cell divisions using endogenous genetic markers.
• To determine the cellular origins and contributions of progenitors to various tissues and germ layers.

Main Methods:

• High-depth whole-genome sequencing to identify somatic single-nucleotide variants (sSNVs).
• Using sSNVs as endogenous barcodes for single-cell lineage reconstruction.
• Targeted sequencing, single-nucleus RNA sequencing, and single-nucleus assay for transposase-accessible chromatin sequencing (snATAC-seq) on human tissues and cells.

Main Results:

• Successfully reconstructed early embryonic cell divisions using sSNVs.
• Demonstrated asymmetric progenitor contributions to extraembryonic tissues, germ layers, and organs.
• Estimated the onset of gastrulation and the number of forebrain founders.

Conclusions:

• Mosaic mutations provide a high-resolution, permanent record of human embryonic development.
• This method allows for detailed lineage tracing in humans.
• Insights into the cellular dynamics of early human development were gained.