XB-ART-58965
Cell Rep
2022 Feb 15;387:110364. doi: 10.1016/j.celrep.2022.110364.
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Uncovering the mesendoderm gene regulatory network through multi-omic data integration.
Jansen C
,
Paraiso KD
,
Zhou JJ
,
Blitz IL
,
Fish MB
,
Charney RM
,
Cho JS
,
Yasuoka Y
,
Sudou N
,
Bright AR
,
Wlizla M
,
Veenstra GJC
,
Taira M
,
Zorn AM
,
Mortazavi A
,
Cho KWY
.
Abstract
Mesendodermal specification is one of the earliest events in embryogenesis, where cells first acquire distinct identities. Cell differentiation is a highly regulated process that involves the function of numerous transcription factors (TFs) and signaling molecules, which can be described with gene regulatory networks (GRNs). Cell differentiation GRNs are difficult to build because existing mechanistic methods are low throughput, and high-throughput methods tend to be non-mechanistic. Additionally, integrating highly dimensional data composed of more than two data types is challenging. Here, we use linked self-organizing maps to combine chromatin immunoprecipitation sequencing (ChIP-seq)/ATAC-seq with temporal, spatial, and perturbation RNA sequencing (RNA-seq) data from Xenopus tropicalis mesendoderm development to build a high-resolution genome scale mechanistic GRN. We recover both known and previously unsuspected TF-DNA/TF-TF interactions validated through reporter assays. Our analysis provides insights into transcriptional regulation of early cell fate decisions and provides a general approach to building GRNs using highly dimensional multi-omic datasets.
PubMed ID: 35172134
Article link: Cell Rep
Grant support: [+]
R01 HD073179 NICHD NIH HHS , S10 OD021718 NIH HHS , P41 HD064556 NICHD NIH HHS , R01 GM126395 NIGMS NIH HHS , S10 RR025496 NCRR NIH HHS , S10 OD010794 NIH HHS , P30 CA062203 NCI NIH HHS , R01 DK123092 NIDDK NIH HHS , R35 GM139617 NIGMS NIH HHS , T32 HD060555 NICHD NIH HHS
Species referenced: Xenopus tropicalis
Genes referenced: bmp4 cer1 ctnnb1 eomes foxa2 foxa4 foxh1 gata4 gata6 gli3 gsc hhex lhx1 mixer nodal nodal1 nodal2 osr1 osr2 otx1 otx2 sebox sia1 smad1 smad2 smad3 sox17a sox17b sox7 tbxt tcf7l1 vegt wnt8a
GO keywords: RNA polymerase II activity [+]
Antibodies: Mix1 Ab1 Sia1 Ab1 Sox7 Ab1 VegT Ab2 Ventx2 Ab1
Morpholinos: foxh1 MO2 sox17a MO5 tcf7l1 MO2
GEO Series: GSE161600: NCBI
Article Images: [+] show captions
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