Grave-to-cradle: human embryonic lineage tracing from the postmortem body

• Published in: Experimental & molecular medicine 2023, 55(0), , pp.13-21
• Main Authors: Choi, Seock Hwan, Ku, Eu Jeong, Choi, Yujin Angelina, Oh, Ji Won
• Format: Article
• Language: English
• Subjects: 13/106; 45/100; 45/23; 631/136/1455; 631/136/2086/1986; 692/698/690; Autopsy; Biomedical and Life Sciences; Biomedicine; Cadavers; Cell Lineage - genetics; Cell migration; Embryos; Fertilization in Vitro; Gene mapping; Genomes; Humans; In vitro fertilization; Medical Biochemistry; Molecular Medicine; Mutation; Nucleotides; Retrospective Studies; Review; Review Article; Stem Cells; Whole genome sequencing; 생화학
• ISSN: 2092-6413; 1226-3613; 2092-6413
• DOI: 10.1038/s12276-022-00912-y

Curiosity concerning the process of human creation has been around for a long time. Relevant questions seemed to be resolved with the knowledge of how cells divide after fertilization obtained through in vitro fertilization experiments. However, we still do not know how human life is created at the cellular level. Recently, the value of cadavers as a resource from which to obtain “normal” cells and tissues has been established, and human research using postmortem bodies has attracted growing scientific attention. As the human genome can be analyzed at the level of nucleotides through whole-genome sequencing, individual cells in a postmortem body can be traced back to determine what developmental processes have transpired from fertilization. These retrospective lineage tracing studies have answered several unsolved questions on how humans are created. This review covers the methodologies utilized in lineage tracing research in a historical context and the conceptual basis for reconstructing the division history of cells in a retrospective manner using postzygotic somatic variants in postmortem tissue. We further highlight answers that postmortem research could potentially address and discuss issues that wait to be solved in the future. Development: Mapping the history of individual cells Identifying all the precursors of an individual cell, called lineage tracing, is allowing researchers to gain a new level of understanding of human development. Cells naturally accumulate non-harmful mutations over their lifetime. Using whole-genome sequencing of individual cells, researchers can track accumulation of these mutations as cells divide and migrate, to make a cell-level map of development. Ji Won Oh at Yonsei University College of Medicine in Seoul, South Korea, and co-workers have reviewed recent developments in lineage tracing performed using individual cells from postmortem bodies. They report that lineage tracing provides insight into the asymmetric contributions made by early cells, and into which cell types build each organ. They hope the field will produce a map of cell divisions and cellular fate from fertilized egg to mature adult, deepening understanding of human development.