Early developmental asymmetries in cell lineage trees in living individuals

Liana Fasching; Yeongjun Jang; Simone Tomasi; Jeremy Schreiner; Livia Tomasini; Melanie V. Brady; Taejeong Bae; Vivekananda Sarangi; Nikolaos Vasmatzis; Yifan Wang; Anna Szekely; Thomas V. Fernandez; James F. Leckman; Alexej Abyzov; Flora M. Vaccarino

doi:10.1126/science.abe0981

Early developmental asymmetries in cell lineage trees in living individuals

Liana Fasching, Yeongjun Jang, Simone Tomasi, Jeremy Schreiner, Livia Tomasini, Melanie V. Brady, Taejeong Bae, Vivekananda Sarangi, Nikolaos Vasmatzis, Yifan Wang, Anna Szekely, Thomas V. Fernandez, James F. Leckman, Alexej Abyzov, Flora M. Vaccarino

Quantitative Health Sciences

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1245-1248
Number of pages	4
Journal	Science
Volume	371
Issue number	6535
DOIs	https://doi.org/10.1126/science.abe0981
State	Published - Mar 19 2021

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title = "Early developmental asymmetries in cell lineage trees in living individuals",

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.",

author = "Liana Fasching and Yeongjun Jang and Simone Tomasi and Jeremy Schreiner and Livia Tomasini and Brady, {Melanie V.} and Taejeong Bae and Vivekananda Sarangi and Nikolaos Vasmatzis and Yifan Wang and Anna Szekely and Fernandez, {Thomas V.} and Leckman, {James F.} and Alexej Abyzov and Vaccarino, {Flora M.}",

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T1 - Early developmental asymmetries in cell lineage trees in living individuals

AU - Fasching, Liana

AU - Jang, Yeongjun

AU - Tomasi, Simone

AU - Schreiner, Jeremy

AU - Tomasini, Livia

AU - Brady, Melanie V.

AU - Bae, Taejeong

AU - Sarangi, Vivekananda

AU - Vasmatzis, Nikolaos

AU - Wang, Yifan

AU - Szekely, Anna

AU - Fernandez, Thomas V.

AU - Leckman, James F.

AU - Abyzov, Alexej

AU - Vaccarino, Flora M.

PY - 2021/3/19

Y1 - 2021/3/19

N2 - 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.

AB - 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.

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Early developmental asymmetries in cell lineage trees in living individuals

Abstract

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