Simultaneous brain cell type and lineage determined by scRNA-seq reveals stereotyped cortical development.
Simultaneous brain cell type and lineage determined by scRNA-seq reveals stereotyped cortical development.
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DOI：
10.1016/j.cels.2022.03.006
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发表时间：
2022-06-15
期刊：
影响因子：
9.3
通讯作者：
中科院分区：
文献类型：
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突变是频繁获得的，因此每个细胞的基因组都记录了它的细胞分裂历史。常见的基因组改变包括杂合性缺失(LOH)。LOH在整个基因组中积累，为推断细胞谱系提供了巨大的编码能力。仅使用小鼠脑细胞的单细胞RNA测序(scRNA-seq)，我们发现跨越多个基因的LOH事件被揭示为单等位基因表达的、构成上杂合的单核苷酸变体(SNV)区域。我们同时根据X染色体失活和LOH事件总数推断细胞谱系、标记的发育时间点，同时根据基因表达模式识别细胞类型。我们的结果与前体细胞通过刻板的扩增和不同的神经发生波产生多种皮质细胞类型是一致的。这种类型的回溯性分析可以结合到scRNA-seq管道中，与确定模式生物谱系的实验方法相比，适用于禁止遗传工程的地方，如人类。仅依靠scRNA-seq分析，Anderson等人。根据基因表达追溯推断细胞类型，通过检测获得性LOH事件重建谱系，并在小鼠大脑发育期间以单细胞分辨率从雌性X染色体失活的时间标记发育有序的细胞分支。
Mutations are acquired frequently, such that each cell’s genome inscribes its history of cell divisions. Common genomic alterations involve loss of heterozygosity (LOH). LOH accumulates throughout the genome, offering large encoding capacity for inferring cell lineage. Using only single cell RNA sequencing (scRNA-seq) of mouse brain cells, we found that LOH events spanning multiple genes are revealed as tracts of monoallelically expressed, constitutionally heterozygous single nucleotide variants (SNVs). We simultaneously inferred cell lineage, marked developmental time points based on X-chromosome inactivation and the total number of LOH events, while identifying cell types from gene expression patterns. Our results are consistent with progenitor cells giving rise to multiple cortical cell types through stereotyped expansion and distinct waves of neurogenesis. This type of retrospective analysis could be incorporated into scRNA-seq pipelines and, compared to experimental approaches for determining lineage in model organisms, is applicable where genetic engineering is prohibited, such as humans. Relying solely on scRNA-seq analysis, Anderson et al. retrospectively infer cell type based on gene expression, reconstruct lineage through detection of acquired LOH events, and temporally mark developmentally ordered cell clades from the timing of X-chromosome inactivation in females, at single cell resolution during mouse brain development.
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影响因子：
48
作者：
Carlson, Cheryl A.;Kas, Arnold;Kirkwood, Robert;Hays, Laura E.;Preston, Bradley D.;Salipante, Stephen J.;Horwitz, Marshall S.
通讯作者：
Horwitz, Marshall S.
正常细胞的基因组测序揭示了发育谱系和突变过程。
影响因子：
64.8
作者：
Behjati, Sam;Huch, Meritxell;van Boxtel, Ruben;Karthaus, Wouter;Wedge, David C.;Tamuri, Asif U.;Martincorena, Inigo;Petljak, Mia;Alexandrov, Ludmil B.;Gundem, Gunes;Tarpey, Patrick S.;Roerink, Sophie;Blokker, Joyce;Maddison, Mark;Mudie, Laura;Robinson, Ben;Nik-Zainal, Serena;Campbell, Peter;Goldman, Nick;van de Wetering, Marc;Cuppen, Edwin;Clevers, Hans;Stratton, Michael R.
通讯作者：
Stratton, Michael R.
影响因子：
9.8
作者：
Borel, Christelle;Ferreira, Pedro G.;Antonarakis, Stylianos E.
通讯作者：
Antonarakis, Stylianos E.
DOI：
10.1126/science.abe0981
发表时间：
2021-03-19
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Fasching L;Jang Y;Tomasi S;Schreiner J;Tomasini L;Brady MV;Bae T;Sarangi V;Vasmatzis N;Wang Y;Szekely A;Fernandez TV;Leckman JF;Abyzov A;Vaccarino FM
通讯作者：
Vaccarino FM
DOI：
10.1126/science.1192280
发表时间：
2010-10-01
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Choate KA;Lu Y;Zhou J;Choi M;Elias PM;Farhi A;Nelson-Williams C;Crumrine D;Williams ML;Nopper AJ;Bree A;Milstone LM;Lifton RP
通讯作者：
Lifton RP