Cambridge scientists uncover new insights into fetal development in humans
Researchers have uncovered new insights into how bodies are formed from a single cell.
The study, by scientists at the Wellcome Sanger Institute, the Wellcome-MRC Cambridge Stem Cell Institute and the University of Cambridge, is the first to describe fetal development in humans by retracing how and when mutations are acquired during pregnancy.
They found higher rates of mutations in early cell divisions - and discovered that the ‘decision’ of whether cells become the fetus or protective tissues like the placenta occurs much earlier than previously thought - at the stage between four and 16 cells.
The work creates an important reference of mutation under normal conditions to aid research into the causes of diseases such as childhood cancers and rare developmental disorders, which often begin in utero.
Dr Anna Ranzoni, a first author of the study from the Wellcome-MRC Cambridge Stem Cell Institute and Department of Haematology at the University of Cambridge, said: “The findings of this study have challenged some of our previous understanding about how the fetus grows from one cell during the earliest stages of life, such as when the embryonic and extra-embryonic tissues diverge. This kind of resolution will be essential if we are to try to pinpoint the origin of diseases that have their roots in development.”
The research, published in Nature, also highlights subtle differences between human and mice biology.
Dr Michael Spencer Chapman, a first author of the study from the Wellcome Sanger Institute, said: “Mice have been an excellent model for studying human development, but there was always the question of whether mouse biology was the same as our biology or merely similar. We found evidence that primitive human blood cells arise from the hypoblast, which is different to mice, settling a question that has been debated for decades.”
For the study, researchers at the Wellcome Sanger Institute and Wellcome-MRC Cambridge Stem Cell Institute collected eight week and eighteen week-old haematopoietic stem and progenitor cells (HSPCs) from human fetal tissue, provided ethically by the Human Developmental Biology Resource, and grew them into 511 single-cell-derived colonies.
DNA from these colonies underwent whole genome sequencing to identify somatic mutations that could be used to trace the lineage of blood cells back to the first division of the embryo.
The researchers then looked for these ‘marker’ mutations in tiny biopsies from other tissues to see when they diverged from the blood cell population.
They found that by week eight of development, cells had acquired 25 mutations and 42 by week 18, indicating a higher rate of mutation in early cell divisions.
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