Spatial Analysis of Single Fiber Cells of the Developing Ocular Lens Reveals Regulated Heterogeneity of Gene Expression.
Spatial Analysis of Single Fiber Cells of the Developing Ocular Lens Reveals Regulated Heterogeneity of Gene Expression.
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DOI：
10.1016/j.isci.2018.11.024
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发表时间：
2018-12-21
期刊：
影响因子：
5.8
通讯作者：
Bhat SP
中科院分区：
文献类型：
--
作者：
Gangalum RK;Kim D;Kashyap RK;Mangul S;Zhou X;Elashoff D;Bhat SP
正在发育的眼睛晶状体为空间转录组学提供了一个特殊的范例。它由高度组织化的长而细长的透明纤维细胞组成，这些纤维细胞从晶状体前上皮（赤道）的边缘分化出来，伴随着晶状体蛋白的高表达，从而产生透明度。因此，每个纤维细胞都是一个光学单元，其折射特性源自其基因活性。在这里，我们通过研究从三种分化状态/区域分离的单纤维细胞中所有已知的 17 种晶状体蛋白和 77 种其他非晶状体蛋白基因的表达来探讨基因活性和表型之间的这种切实关系，使我们能够在单细胞水平上跟踪分子进展。数据表明，皮质纤维中的基因活性高度可变，介于新生纤维细胞转录和终末分化纤维细胞转录之间。这些数据表明，所谓的随机、高度异质的基因活性是实现功能表型的受调节中间体。转录异质性参与上皮细胞向纤维细胞的分化 早期晶状体蛋白表达表明终末纤维分化的决定性 高折射率增量蛋白的基因协调表达 分子异质性使每个纤维细胞成为独特的折射单位发育生物学；组学；生物科学研究方法
The developing eye lens presents an exceptional paradigm for spatial transcriptomics. It is composed of highly organized long, slender transparent fiber cells, which differentiate from the edges of the anterior epithelium of the lens (equator), attended by high expression of crystallins, which generates transparency. Every fiber cell, therefore, is an optical unit whose refractive properties derive from its gene activity. Here, we probe this tangible relationship between the gene activity and the phenotype by studying the expression of all known 17 crystallins and 77 other non-crystallin genes in single fiber cells isolated from three states/regions of differentiation, allowing us to follow molecular progression at the single-cell level. The data demonstrate highly variable gene activity in cortical fibers, interposed between the nascent and the terminally differentiated fiber cell transcription. These data suggest that the so-called stochastic, highly heterogeneous gene activity is a regulated intermediate in the realization of a functional phenotype. Transcriptional heterogeneity attends epithelial cell differentiation to fiber cells Early crystallin expression suggests determinism in terminal fiber differentiation Genes for high-refractive-index-increment proteins are coordinately expressed Molecular heterogeneity makes every fiber cell a unique refractive unit Cell Biology; Developmental Biology; Omics; Biological Sciences Research Methodologies
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影响因子：
64.8
作者：
Halpern KB;Shenhav R;Matcovitch-Natan O;Toth B;Lemze D;Golan M;Massasa EE;Baydatch S;Landen S;Moor AE;Brandis A;Giladi A;Avihail AS;David E;Amit I;Itzkovitz S
通讯作者：
Itzkovitz S
影响因子：
3.4
作者：
Chakraborty, Ranjay;Lacy, Kip D.;Tan, Christopher C.;Park, Han Na;Pardue, Machelle T.
通讯作者：
Pardue, Machelle T.
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46.9
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影响因子：
17.8
作者：
Iribarren, Rafael
通讯作者：
Iribarren, Rafael
影响因子：
4.6
作者：
Kobayashi M;Oshima S;Maeyashiki C;Nibe Y;Otsubo K;Matsuzawa Y;Nemoto Y;Nagaishi T;Okamoto R;Tsuchiya K;Nakamura T;Watanabe M
通讯作者：
Watanabe M