Neighbor-specific gene expression revealed from physically interacting cells during mouse embryonic development.
Neighbor-specific gene expression revealed from physically interacting cells during mouse embryonic development.
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DOI：
10.1073/pnas.2205371120
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发表时间：
2023-01-10
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
--
作者：
Physical contact between neighboring cells is known to induce transcriptional changes in the interacting partners. Accurate measurement of these cell–cell contact-based influences on the transcriptome is a very difficult experimental task. However, determining such transcriptional changes will highly enhance our understanding for the developmental processes. Current scRNA-seq technology isolates the tissue into individual cells, making it hard to determine the potential transcriptomic changes due to cell-cell interactions. Here, we combined PIC-seq and computational algorithms to identify cell type contact-dependent transcriptional profiles focusing on endoderm development. We have computationally identified and experimentally validated specific gene expression patterns depending on the presence of specific neighboring cell types. Our study suggests a new approach to disentangle the role of cell–cell interactions during embryogenesis. Development of multicellular organisms is orchestrated by persistent cell–cell communication between neighboring partners. Direct interaction between different cell types can induce molecular signals that dictate lineage specification and cell fate decisions. Current single-cell RNA-seq technology cannot adequately analyze cell–cell contact-dependent gene expression, mainly due to the loss of spatial information. To overcome this obstacle and resolve cell–cell contact-specific gene expression during embryogenesis, we performed RNA sequencing of physically interacting cells (PIC-seq) and assessed them alongside similar single-cell transcriptomes derived from developing mouse embryos between embryonic day (E) 7.5 and E9.5. Analysis of the PIC-seq data identified gene expression signatures that were dependent on the presence of specific neighboring cell types. Our computational predictions, validated experimentally, demonstrated that neural progenitor (NP) cells upregulate Lhx5 and Nkx2-1 genes, when exclusively interacting with definitive endoderm (DE) cells. Moreover, there was a reciprocal impact on the transcriptome of DE cells, as they tend to upregulate Rax and Gsc when in contact with NP cells. Using individual cell transcriptome data, we formulated a means of computationally predicting the impact of one cell type on the transcriptome of its neighboring cell types. We have further developed a distinctive spatial-t-distributed stochastic neighboring embedding to display the pseudospatial distribution of cells in a 2-dimensional space. In summary, we describe an innovative approach to study contact-specific gene regulation during embryogenesis.
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影响因子：
64.8
作者：
Cao, Junyue;Spielmann, Malte;Shendure, Jay
通讯作者：
Shendure, Jay
影响因子：
2.7
作者：
Hansson, Mattias;Olesen, Dorthe R.;Peterslund, Janny M. L.;Engberg, Nina;Kahn, Morten;Winzi, Maria;Klein, Tino;Maddox-Hyttel, Poul;Serup, Palle
通讯作者：
Serup, Palle
DOI：
10.1126/science.1247651
发表时间：
2014-02-14
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Jaitin DA;Kenigsberg E;Keren-Shaul H;Elefant N;Paul F;Zaretsky I;Mildner A;Cohen N;Jung S;Tanay A;Amit I
通讯作者：
Amit I
影响因子：
46.9
作者：
Giladi, Amir;Cohen, Merav;Amit, Ido
通讯作者：
Amit, Ido
影响因子：
2.6
作者：
Belo, JA;Bouwmeester, T;De Robertis, EM
通讯作者：
De Robertis, EM