Somatic mutation in single human neurons tracks developmental and transcriptional history

被引：380

作者：

Lodato, Michael A. ^{[1
,2
,3
,4
,5
]}

Woodworth, Mollie B. ^{[1
,2
,3
,4
,5
]}

Lee, Semin ^{[6
]}

Evrony, Gilad D. ^{[1
,2
,3
,4
,5
]}

Mehta, Bhaven K. ^{[1
,2
,3
,4
,5
]}

Karger, Amir ^{[7
]}

Lee, Soohyun ^{[6
]}

Chittenden, Thomas W. ^{[7
,8
]}

D'Gama, Alissa M. ^{[1
,2
,3
,4
,5
]}

Cai, Xuyu ^{[1
,2
,3
,4
,5
]}

Luquette, Lovelace J. ^{[6
]}

Lee, Eunjung ^{[6
,9
]}

Park, Peter J. ^{[6
,9
]}

Walsh, Christopher A. ^{[1
,2
,3
,4
,5
]}

机构：

[1] Boston Childrens Hosp, Manton Ctr Orphan Dis, Div Genet & Genom, Boston, MA USA

[2] Boston Childrens Hosp, Howard Hughes Med Inst, Boston, MA USA

[3] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA

[5] Broad Inst MIT & Harvard, Cambridge, MA USA

[6] Harvard Univ, Sch Med, Dept Biomed Informat, Boston, MA 02452 USA

[7] Harvard Univ, Sch Med, Res Comp, Boston, MA USA

[8] Complex Biol Syst Alliance, N Andover, MA USA

[9] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA

来源：

SCIENCE | 2015年 / 350卷 / 6256期

关键词：

COPY-NUMBER VARIATION; GENOME; CANCER; CELL; MOSAICISM; LANDSCAPE;

D O I：

10.1126/science.aab1785

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Neurons live for decades in a postmitotic state, their genomes susceptible to DNA damage. Here we survey the landscape of somatic single-nucleotide variants (SNVs) in the human brain. We identified thousands of somatic SNVs by single-cell sequencing of 36 neurons from the cerebral cortex of three normal individuals. Unlike germline and cancer SNVs, which are often caused by errors in DNA replication, neuronal mutations appear to reflect damage during active transcription. Somatic mutations create nested lineage trees, allowing them to be dated relative to developmental landmarks and revealing a polyclonal architecture of the human cerebral cortex. Thus, somatic mutations in the brain represent a durable and ongoing record of neuronal life history, from development through postmitotic function.

引用

页码：94 / 98

页数：5

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