Single-cell and spatial transcriptomics reveal somitogenesis in gastruloids. 2020

Susanne C van den Brink, and Anna Alemany, and Vincent van Batenburg, and Naomi Moris, and Marloes Blotenburg, and Judith Vivié, and Peter Baillie-Johnson, and Jennifer Nichols, and Katharina F Sonnen, and Alfonso Martinez Arias, and Alexander van Oudenaarden
Oncode Institute, Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center Utrecht, Utrecht, The Netherlands. s.c.vandenbrink@gmail.com.

Gastruloids are three-dimensional aggregates of embryonic stem cells that display key features of mammalian development after implantation, including germ-layer specification and axial organization1-3. To date, the expression pattern of only a small number of genes in gastruloids has been explored with microscopy, and the extent to which genome-wide expression patterns in gastruloids mimic those in embryos is unclear. Here we compare mouse gastruloids with mouse embryos using single-cell RNA sequencing and spatial transcriptomics. We identify various embryonic cell types that were not previously known to be present in gastruloids, and show that key regulators of somitogenesis are expressed similarly between embryos and gastruloids. Using live imaging, we show that the somitogenesis clock is active in gastruloids and has dynamics that resemble those in vivo. Because gastruloids can be grown in large quantities, we performed a small screen that revealed how reduced FGF signalling induces a short-tail phenotype in embryos. Finally, we demonstrate that embedding in Matrigel induces gastruloids to generate somites with the correct rostral-caudal patterning, which appear sequentially in an anterior-to-posterior direction over time. This study thus shows the power of gastruloids as a model system for exploring development and somitogenesis in vitro in a high-throughput manner.

UI MeSH Term Description Entries
D007797 Laminin Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. Merosin,Glycoprotein GP-2,Laminin M,Laminin M Chain,Chain, Laminin M,Glycoprotein GP 2,M Chain, Laminin
D008297 Male Males
D009940 Organoids An organization of cells into an organ-like structure. Organoids can be generated in culture, e.g., self-organized three-dimensional tissue structures derived from STEM CELLS (see MICROPHYSIOLOGICAL SYSTEMS). They are also found in certain NEOPLASMS. Organoid
D011509 Proteoglycans Glycoproteins which have a very high polysaccharide content. Proteoglycan,Proteoglycan Type H
D003094 Collagen A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH). Avicon,Avitene,Collagen Felt,Collagen Fleece,Collagenfleece,Collastat,Dermodress,Microfibril Collagen Hemostat,Pangen,Zyderm,alpha-Collagen,Collagen Hemostat, Microfibril,alpha Collagen
D004338 Drug Combinations Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture. Drug Combination,Combination, Drug,Combinations, Drug
D004622 Embryo, Mammalian The entity of a developing mammal (MAMMALS), generally from the cleavage of a ZYGOTE to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the FETUS. Embryonic Structures, Mammalian,Mammalian Embryo,Mammalian Embryo Structures,Mammalian Embryonic Structures,Embryo Structure, Mammalian,Embryo Structures, Mammalian,Embryonic Structure, Mammalian,Embryos, Mammalian,Mammalian Embryo Structure,Mammalian Embryonic Structure,Mammalian Embryos,Structure, Mammalian Embryo,Structure, Mammalian Embryonic,Structures, Mammalian Embryo,Structures, Mammalian Embryonic
D005260 Female Females
D005775 Gastrula The developmental stage that follows BLASTULA or BLASTOCYST. It is characterized by the morphogenetic cell movements including invagination, ingression, and involution. Gastrulation begins with the formation of the PRIMITIVE STREAK, and ends with the formation of three GERM LAYERS, the body plan of the mature organism. Archenteron,Blastopore,Gastrocoele,Primitive Gut,Archenterons,Blastopores,Gastrocoeles,Gastrulas,Gut, Primitive,Guts, Primitive,Primitive Guts
D000066450 Mouse Embryonic Stem Cells PLURIPOTENT STEM CELLS derived from the BLASTOCYST INNER CELL MASS of day 3.5 mouse embryos. mESC,Cells, Mouse Embryonic Stem,Mouse Embryonic Stem Cell,Stem Cells, Mouse Embryonic,mESCs

Related Publications

Susanne C van den Brink, and Anna Alemany, and Vincent van Batenburg, and Naomi Moris, and Marloes Blotenburg, and Judith Vivié, and Peter Baillie-Johnson, and Jennifer Nichols, and Katharina F Sonnen, and Alfonso Martinez Arias, and Alexander van Oudenaarden
November 2021, Nature cell biology,
Susanne C van den Brink, and Anna Alemany, and Vincent van Batenburg, and Naomi Moris, and Marloes Blotenburg, and Judith Vivié, and Peter Baillie-Johnson, and Jennifer Nichols, and Katharina F Sonnen, and Alfonso Martinez Arias, and Alexander van Oudenaarden
June 2023, BMC biology,
Susanne C van den Brink, and Anna Alemany, and Vincent van Batenburg, and Naomi Moris, and Marloes Blotenburg, and Judith Vivié, and Peter Baillie-Johnson, and Jennifer Nichols, and Katharina F Sonnen, and Alfonso Martinez Arias, and Alexander van Oudenaarden
February 2023, Immunity,
Susanne C van den Brink, and Anna Alemany, and Vincent van Batenburg, and Naomi Moris, and Marloes Blotenburg, and Judith Vivié, and Peter Baillie-Johnson, and Jennifer Nichols, and Katharina F Sonnen, and Alfonso Martinez Arias, and Alexander van Oudenaarden
January 2020, Nature cell biology,
Susanne C van den Brink, and Anna Alemany, and Vincent van Batenburg, and Naomi Moris, and Marloes Blotenburg, and Judith Vivié, and Peter Baillie-Johnson, and Jennifer Nichols, and Katharina F Sonnen, and Alfonso Martinez Arias, and Alexander van Oudenaarden
January 2022, F1000Research,
Susanne C van den Brink, and Anna Alemany, and Vincent van Batenburg, and Naomi Moris, and Marloes Blotenburg, and Judith Vivié, and Peter Baillie-Johnson, and Jennifer Nichols, and Katharina F Sonnen, and Alfonso Martinez Arias, and Alexander van Oudenaarden
November 2022, Clinical and translational medicine,
Susanne C van den Brink, and Anna Alemany, and Vincent van Batenburg, and Naomi Moris, and Marloes Blotenburg, and Judith Vivié, and Peter Baillie-Johnson, and Jennifer Nichols, and Katharina F Sonnen, and Alfonso Martinez Arias, and Alexander van Oudenaarden
April 2024, The Journal of investigative dermatology,
Susanne C van den Brink, and Anna Alemany, and Vincent van Batenburg, and Naomi Moris, and Marloes Blotenburg, and Judith Vivié, and Peter Baillie-Johnson, and Jennifer Nichols, and Katharina F Sonnen, and Alfonso Martinez Arias, and Alexander van Oudenaarden
December 2022, Lab on a chip,
Susanne C van den Brink, and Anna Alemany, and Vincent van Batenburg, and Naomi Moris, and Marloes Blotenburg, and Judith Vivié, and Peter Baillie-Johnson, and Jennifer Nichols, and Katharina F Sonnen, and Alfonso Martinez Arias, and Alexander van Oudenaarden
June 2024, The Journal of pathology,
Susanne C van den Brink, and Anna Alemany, and Vincent van Batenburg, and Naomi Moris, and Marloes Blotenburg, and Judith Vivié, and Peter Baillie-Johnson, and Jennifer Nichols, and Katharina F Sonnen, and Alfonso Martinez Arias, and Alexander van Oudenaarden
July 2021, Science (New York, N.Y.),
Copied contents to your clipboard!