Neighbor-specific gene expression revealed from physically interacting cells during mouse embryonic development
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Neighbor-specific gene expression revealed from physically interacting cells during mouse embryonic development. / Kim, Junil; Rothová, Michaela Mrugala; Madan, Esha; Rhee, Siyeon; Weng, Guangzheng; Palma, António M.; Liao, Linbu; David, Eyal; Amit, Ido; Hajkarim, Morteza Chalabi; Vudatha, Vignesh; Gutiérrez-García, Andrés; Moreno, Eduardo; Winn, Robert; Trevino, Jose; Fisher, Paul B.; Brickman, Joshua M.; Gogna, Rajan; Won, Kyoung Jae.
I: Proceedings of the National Academy of Sciences of the United States of America, Bind 120, Nr. 2, e2205371120, 2023.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Neighbor-specific gene expression revealed from physically interacting cells during mouse embryonic development
AU - Kim, Junil
AU - Rothová, Michaela Mrugala
AU - Madan, Esha
AU - Rhee, Siyeon
AU - Weng, Guangzheng
AU - Palma, António M.
AU - Liao, Linbu
AU - David, Eyal
AU - Amit, Ido
AU - Hajkarim, Morteza Chalabi
AU - Vudatha, Vignesh
AU - Gutiérrez-García, Andrés
AU - Moreno, Eduardo
AU - Winn, Robert
AU - Trevino, Jose
AU - Fisher, Paul B.
AU - Brickman, Joshua M.
AU - Gogna, Rajan
AU - Won, Kyoung Jae
N1 - Publisher Copyright: Copyright © 2023 the Author(s).
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - contact-specific expression
KW - mouse embryonic development
KW - PIC-seq
KW - single-cell RNA sequencing
KW - spatial-tSNE
U2 - 10.1073/pnas.2205371120
DO - 10.1073/pnas.2205371120
M3 - Journal article
C2 - 36595695
AN - SCOPUS:85145429535
VL - 120
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 2
M1 - e2205371120
ER -
ID: 372960045