Ori Fridlich¹, Agnes Klochendler¹, Sorina Grisaru-Granovsky², Benjamin Glaser³, Ruth Shemer¹, Yuval Dor¹

¹Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem.

²Division of Maternal Fetal Medicine, Shaare Zedek Medical Center Jerusalem

³Endocrine services, Hadassah-Hebrew University Medical Center, Jerusalem

Dying cells release small fragments of DNA into the bloodstream. This Cell-free circulating DNA (cfDNA) is emerging as a powerful biomarker in prenatal diagnosis (detection of fetal mutations), cancer (monitoring tumor dynamics) and transplantation medicine (detection of graft rejection).

We have developed an approach to identify the tissues origins of cfDNA, based on tissue-specific methylation patterns that are retained in circulating DNA fragments. The method allows to infer the rates of cell death in specific human tissues.

Here we apply this method to study fetal tissue dynamics, using tissue-specific cfDNA methylation markers in cord blood. We identify cfDNA derived from brain, colon and pancreas in the cord blood of healthy, term babies, likely reflecting cell death during normal late embryonic development. Future studies will examine fetal tissue dynamics after caesarian delivery and in different fetal ages. The approach opens a minimally-invasive window into normal and pathological human fetal development.