RT Journal Article
SR Electronic
T1 Characterizing the Emergence of Liver and Gallbladder from the Embryonic Endoderm through Single-Cell RNA-Seq
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 718775
DO 10.1101/718775
A1 Tianhao Mu
A1 Liqin Xu
A1 Yu Zhong
A1 Xinyu Liu
A1 Zhikun Zhao
A1 Chaoben Huang
A1 Xiaofeng Lan
A1 Chengchen Lufei
A1 Yi Zhou
A1 Yixun Su
A1 Luang Xu
A1 Miaomiao Jiang
A1 Hongpo Zhou
A1 Xinxin Lin
A1 Liang Wu
A1 Siqi Peng
A1 Shiping Liu
A1 Susanne Brix
A1 Michael Dean
A1 Norris R. Dunn
A1 Kenneth S. Zaret
A1 Xin-Yuan Fu
A1 Yong Hou
YR 2019
UL http://biorxiv.org/content/early/2019/07/30/718775.abstract
AB The liver and gallbladder are among the most important internal organs derived from the endoderm. Several inductive signals regulate liver development, yet the pure nascent hepatic and gallbladder cells are unable to be isolated due to limited cell markers and cell numbers. The transcriptome networks of the hepatic lineage in the endoderm, and how the gallbladder differentiates from the adjacent endoderm population, are not fully understood. Using a transgenic Foxa2eGFP reporter mouse line, we performed deep single-cell RNA sequencing on 1,966 individual cells, including nascent hepatic and gallbladder cells, isolated from the endoderm and hepatic regions from ten embryonic stages, ranging from day E7.5 to E15.5. We identified the embryonic liver developmental trajectory from primitive streak to hepatoblasts and characterized the transcriptome of the hepatic lineage. During pre-hepatogenesis (5-6 somite stage), we have identified two groups of foregut endoderm cells, one derived from visceral endoderm and the second derived from primitive streak via a mesenchymal-epithelial transition (MET). During the liver specification stages, liver primordium was identified to share both foregut and liver features. We also documented dynamic gene expression during the epithelial-hepatic transition (EHT). Six gene groups were found to switch on or off at different stages during liver specification. Importantly, we found that RXR complex signaling and newly identified transcription factors associated with liver specification. Moreover, we revealed the gallbladder primordium cells at E9.5 and found genes that transcriptionally distinguish them from the liver primordium. The present data provides a high-resolution resource and critical insights for understanding the emergence of the endoderm, liver and gallbladder development.METmesenchymal-epithelial transitionEHTepithelial-hepatic transitionE7.5Embryonic day 7.5MIRALCSmicrowell full-length mRNA amplification and library construction systemRPKMReads Per Kilobase per Million mapped readst-SNET-distributed Stochastic Neighbor EmbeddingPSprimitive streakFGforegut endodermVEvisceral endodermNTneural tubeNCnotochordIPAIngenuity pathway analysisECMextracellular matrixM scoremesenchymal scoreE scoreepithelial scoreGTgut tubeLPliver primordiumLBliver budGBPgallbladder primordiumRaceIDrare cell type identificationL1gene group Liver 1L2gene group Liver 2L3gene group Liver 3G1gene group Gut tube 1G2gene group Gut tube 2G3gene group Gut tube 3LXR/RXRliver X receptors/retinoid X receptorsTFtranscription factorFACSFluorescence-activated cell sorting