High-resolution transcriptional and morphogenetic profiling of cells from micropatterned human ESC gastruloid cultures.

ELife
Kyaw Thu MinnLilianna Solnica-Krezel

Abstract

During mammalian gastrulation, germ layers arise and are shaped into the body plan while extraembryonic layers sustain the embryo. Human embryonic stem cells, cultured with BMP4 on extracellular matrix micro-discs, reproducibly differentiate into gastruloids, expressing markers of germ layers and extraembryonic cells in radial arrangement. Using single-cell RNA sequencing and cross-species comparisons with mouse, cynomolgus monkey gastrulae, and post-implantation human embryos, we reveal that gastruloids contain cells transcriptionally similar to epiblast, ectoderm, mesoderm, endoderm, primordial germ cells, trophectoderm, and amnion. Upon gastruloid dissociation, single cells reseeded onto micro-discs were motile and aggregated with the same but segregated from distinct cell types. Ectodermal cells segregated from endodermal and extraembryonic but mixed with mesodermal cells. Our work demonstrates that the gastruloid system models primate-specific features of embryogenesis, and that gastruloid cells exhibit evolutionarily conserved sorting behaviors. This work generates a resource for transcriptomes of human extraembryonic and embryonic germ layers differentiated in a stereotyped arrangement.

References

Jan 1, 1990·Annual Review of Biochemistry·M Takeichi
Jan 1, 1997·Developmental Biology·G L RadiceR O Hynes
Feb 12, 1998·Mechanisms of Development·P P Tam, R R Behringer
Feb 27, 1999·Genes & Development·K A LawsonB L Hogan
Mar 17, 2001·Nature Reviews. Genetics·E M De RobertisO Wessely
Jun 22, 2001·Nature·J BrennanE J Robertson
Jun 29, 2005·Development·Alejandro Barrallo-Gimeno, M Angela Nieto
Feb 7, 2006·Gene Expression Patterns : GEP·Scott E KlewerTodd D Camenisch
Sep 11, 2007·Developmental Biology·Rachel M Warga, Donald A Kane
Mar 28, 2008·Nature Cell Biology·M KriegC-P Heisenberg
Nov 6, 2008·Cell Stem Cell·Derk ten BergeRoel Nusse
Jan 9, 2009·Nature Reviews. Molecular Cell Biology·Sebastian J Arnold, Elizabeth J Robertson
Jan 13, 2010·Cold Spring Harbor Perspectives in Biology·Alexander F Schier
Feb 12, 2010·Cold Spring Harbor Protocols·Manuel Théry, Matthieu Piel
Apr 7, 2010·The Journal of Clinical Investigation·Katie Cockburn, Janet Rossant
Sep 21, 2010·The European Physical Journal. E, Soft Matter·A V KlopperC-P Heisenberg
Nov 30, 2010·Cell Stem Cell·Maxim A VodyanikIgor I Slukvin
Apr 20, 2011·Current Topics in Developmental Biology·S F Gabby Krens, Carl-Philipp Heisenberg
Dec 16, 2011·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Margot WilliamsAnn Sutherland
Jun 30, 2012·Nature Methods·Johannes SchindelinAlbert Cardona
Jul 19, 2012·Annual Review of Cell and Developmental Biology·Lila Solnica-Krezel, Diane S Sepich
Feb 23, 2013·The Journal of Reproduction and Development·Hanako BaiKazuhiko Imakawa
Apr 17, 2013·BMC Bioinformatics·Edward Y ChenAvi Ma'ayan
Feb 20, 2014·Development·Marc Amoyel, Erika A Bach
Jun 30, 2014·Nature Methods·Aryeh WarmflashAli H Brivanlou
Aug 21, 2014·Development·François Fagotto
Dec 9, 2014·Cell Adhesion & Migration·Francois FagottoNazanin Rohani
Mar 4, 2015·Current Topics in Developmental Biology·François Fagotto
May 29, 2015·Nature Methods·Loic A RoyerEugene W Myers
Aug 22, 2015·Development·Paul BlakeleyKathy K Niakan
Dec 17, 2015·Bioinformatics·Philipp AngererFlorian Buettner
May 5, 2016·Nature·Alessia DeglincertiAli H Brivanlou

❮ Previous
Next ❯

Citations

Jan 15, 2021·International Journal of Molecular Sciences·Margit RosnerMarkus Hengstschläger
Jan 24, 2021·Developmental Biology·Sabitri GhimireAlfonso Martinez Arias
Mar 24, 2021·Developmental Biology·Jake Cornwall-Scoones, Magdalena Zernicka-Goetz
Dec 23, 2020·Developmental Biology·Alexandra Schauer, Carl-Philipp Heisenberg
Apr 11, 2021·Nature Cell Biology·Min YangNorbert Gleicher
May 13, 2021·Stem Cell Reports·Lizhong Liu, Aryeh Warmflash
Nov 15, 2021·Journal of Molecular Biology·Yunping Chen, Yue Shao

❮ Previous
Next ❯

Methods Mentioned

BETA
scRNA-seq
RNA-seq
Chip

Software Mentioned

FindTranferAnchors
Seurat R
Fiji
ClearVolume
Cell Ranger
Graphpad Prism
Pseudotime
FindTransferAnchors
Enrichr
FindAllMarkers

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.