Liana Fasching1, Yeongjun Jang2, Simone Tomasi1, Jeremy Schreiner1, Livia Tomasini1, Melanie V Brady1, Taejeong Bae2, Vivekananda Sarangi2, Nikolaos Vasmatzis2, Yifan Wang2, Anna Szekely3, Thomas V Fernandez1,4, James F Leckman1,4, Alexej Abyzov5, Flora M Vaccarino6,7,8. 1. Child Study Center, Yale University, New Haven, CT 06520, USA. 2. Department of Quantitative Health Sciences, Center for Individualized Medicine, Mayo Clinic, Rochester, MN 55905, USA. 3. Department of Neurology, Yale University, New Haven, CT 06520, USA. 4. Department of Psychiatry, Yale University, New Haven, CT 06520, USA. 5. Department of Quantitative Health Sciences, Center for Individualized Medicine, Mayo Clinic, Rochester, MN 55905, USA. abyzov.alexej@mayo.edu flora.vaccarino@yale.edu. 6. Child Study Center, Yale University, New Haven, CT 06520, USA. abyzov.alexej@mayo.edu flora.vaccarino@yale.edu. 7. Department of Neuroscience, Yale University, New Haven, CT 06520, USA. 8. Yale Kavli Institute for Neuroscience, New Haven, CT 06520, USA.
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.
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 pan class="Species">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.
Authors: Taejeong Bae; Liana Fasching; Yifan Wang; Joo Heon Shin; Milovan Suvakov; Yeongjun Jang; Scott Norton; Caroline Dias; Jessica Mariani; Alexandre Jourdon; Feinan Wu; Arijit Panda; Reenal Pattni; Yasmine Chahine; Rebecca Yeh; Rosalinda C Roberts; Anita Huttner; Joel E Kleinman; Thomas M Hyde; Richard E Straub; Christopher A Walsh; Alexander E Urban; James F Leckman; Daniel R Weinberger; Flora M Vaccarino; Alexej Abyzov Journal: Science Date: 2022-07-28 Impact factor: 63.714