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Cells & Development Sep 2021Early in animal development many cells are conditionally specified based on observations that those cells can be directed toward alternate fates. The endomesoderm is so... (Review)
Review
Early in animal development many cells are conditionally specified based on observations that those cells can be directed toward alternate fates. The endomesoderm is so named because early specification produces cells that often have been observed to simultaneously express both early endoderm and mesoderm transcription factors. Experiments with these cells demonstrate that their progeny can directed entirely toward endoderm or mesoderm, whereas normally they establish both germ layers. This review examines the mechanisms that initiate the conditional endomesoderm state, its metastability, and the mechanisms that resolve that state into definitive endoderm and mesoderm.
Topics: Animals; Body Patterning; Endoderm; Humans; Mesoderm; Models, Biological; Sea Urchins; Signal Transduction
PubMed: 34245941
DOI: 10.1016/j.cdev.2021.203716 -
Nature Communications Sep 2020Understanding cell types and mechanisms of dental growth is essential for reconstruction and engineering of teeth. Therefore, we investigated cellular composition of...
Understanding cell types and mechanisms of dental growth is essential for reconstruction and engineering of teeth. Therefore, we investigated cellular composition of growing and non-growing mouse and human teeth. As a result, we report an unappreciated cellular complexity of the continuously-growing mouse incisor, which suggests a coherent model of cell dynamics enabling unarrested growth. This model relies on spatially-restricted stem, progenitor and differentiated populations in the epithelial and mesenchymal compartments underlying the coordinated expansion of two major branches of pulpal cells and diverse epithelial subtypes. Further comparisons of human and mouse teeth yield both parallelisms and differences in tissue heterogeneity and highlight the specifics behind growing and non-growing modes. Despite being similar at a coarse level, mouse and human teeth reveal molecular differences and species-specific cell subtypes suggesting possible evolutionary divergence. Overall, here we provide an atlas of human and mouse teeth with a focus on growth and differentiation.
Topics: Adolescent; Adult; Animals; Cell Differentiation; Epithelial Cells; Female; Gene Expression Regulation, Developmental; Genetic Heterogeneity; Humans; Incisor; Male; Mesoderm; Mice; Mice, Inbred C57BL; Models, Animal; Molar; Odontoblasts; Stem Cells; Tooth; Young Adult
PubMed: 32968047
DOI: 10.1038/s41467-020-18512-7 -
Nature Feb 2024Implantation of the human embryo begins a critical developmental stage that comprises profound events including axis formation, gastrulation and the emergence of...
Implantation of the human embryo begins a critical developmental stage that comprises profound events including axis formation, gastrulation and the emergence of haematopoietic system. Our mechanistic knowledge of this window of human life remains limited due to restricted access to in vivo samples for both technical and ethical reasons. Stem cell models of human embryo have emerged to help unlock the mysteries of this stage. Here we present a genetically inducible stem cell-derived embryoid model of early post-implantation human embryogenesis that captures the reciprocal codevelopment of embryonic tissue and the extra-embryonic endoderm and mesoderm niche with early haematopoiesis. This model is produced from induced pluripotent stem cells and shows unanticipated self-organizing cellular programmes similar to those that occur in embryogenesis, including the formation of amniotic cavity and bilaminar disc morphologies as well as the generation of an anterior hypoblast pole and posterior domain. The extra-embryonic layer in these embryoids lacks trophoblast and shows advanced multilineage yolk sac tissue-like morphogenesis that harbours a process similar to distinct waves of haematopoiesis, including the emergence of erythroid-, megakaryocyte-, myeloid- and lymphoid-like cells. This model presents an easy-to-use, high-throughput, reproducible and scalable platform to probe multifaceted aspects of human development and blood formation at the early post-implantation stage. It will provide a tractable human-based model for drug testing and disease modelling.
Topics: Humans; Embryo Implantation; Embryonic Development; Endoderm; Germ Layers; Yolk Sac; Mesoderm; Hematopoiesis; Induced Pluripotent Stem Cells; Amnion; Embryoid Bodies; Cell Lineage; Developmental Biology
PubMed: 38092041
DOI: 10.1038/s41586-023-06914-8 -
Nature Communications Jan 2024Embryonic cells exhibit diverse metabolic states. Recent studies have demonstrated that metabolic reprogramming drives changes in cell identity by affecting gene...
Embryonic cells exhibit diverse metabolic states. Recent studies have demonstrated that metabolic reprogramming drives changes in cell identity by affecting gene expression. However, the connection between cellular metabolism and gene expression remains poorly understood. Here we report that glycolysis-regulated histone lactylation couples the metabolic state of embryonic cells with chromatin organization and gene regulatory network (GRN) activation. We found that lactylation marks genomic regions of glycolytic embryonic tissues, like the neural crest (NC) and pre-somitic mesoderm. Histone lactylation occurs in the loci of NC genes as these cells upregulate glycolysis. This process promotes the accessibility of active enhancers and the deployment of the NC GRN. Reducing the deposition of the mark by targeting LDHA/B leads to the downregulation of NC genes and the impairment of cell migration. The deposition of lactyl-CoA on histones at NC enhancers is supported by a mechanism that involves transcription factors SOX9 and YAP/TEAD. These findings define an epigenetic mechanism that integrates cellular metabolism with the GRNs that orchestrate embryonic development.
Topics: Histones; Gene Regulatory Networks; Transcription Factors; Embryonic Development; Mesoderm
PubMed: 38167340
DOI: 10.1038/s41467-023-44121-1 -
Cell Feb 2024Transcription factors (TFs) can define distinct cellular identities despite nearly identical DNA-binding specificities. One mechanism for achieving regulatory...
Transcription factors (TFs) can define distinct cellular identities despite nearly identical DNA-binding specificities. One mechanism for achieving regulatory specificity is DNA-guided TF cooperativity. Although in vitro studies suggest that it may be common, examples of such cooperativity remain scarce in cellular contexts. Here, we demonstrate how "Coordinator," a long DNA motif composed of common motifs bound by many basic helix-loop-helix (bHLH) and homeodomain (HD) TFs, uniquely defines the regulatory regions of embryonic face and limb mesenchyme. Coordinator guides cooperative and selective binding between the bHLH family mesenchymal regulator TWIST1 and a collective of HD factors associated with regional identities in the face and limb. TWIST1 is required for HD binding and open chromatin at Coordinator sites, whereas HD factors stabilize TWIST1 occupancy at Coordinator and titrate it away from HD-independent sites. This cooperativity results in the shared regulation of genes involved in cell-type and positional identities and ultimately shapes facial morphology and evolution.
Topics: Basic Helix-Loop-Helix Transcription Factors; Binding Sites; DNA; DNA-Binding Proteins; Gene Expression Regulation; Mesoderm; Transcription Factors; Humans; Animals; Mice; Extremities; Embryonic Development
PubMed: 38262408
DOI: 10.1016/j.cell.2023.12.032 -
Cells & Development Dec 2021Early in animal development many cells are conditionally specified based on observations that those cells can be directed toward alternate fates. The endomesoderm is so... (Review)
Review
Early in animal development many cells are conditionally specified based on observations that those cells can be directed toward alternate fates. The endomesoderm is so named because early specification produces cells that often have been observed to simultaneously express both early endoderm and mesoderm transcription factors. Experiments with these cells demonstrate that their progeny can directed entirely toward endoderm or mesoderm, whereas normally they establish both germ layers. This review examines the mechanisms that initiate the conditional endomesoderm state, its metastability, and the mechanisms that resolve that state into definitive endoderm and mesoderm.
Topics: Animals; Embryo, Nonmammalian; Endoderm; Mesoderm; Sea Urchins; Signal Transduction
PubMed: 34610899
DOI: 10.1016/j.cdev.2021.203731 -
Development (Cambridge, England) Jun 2020The lateral plate mesoderm (LPM) forms the progenitor cells that constitute the heart and cardiovascular system, blood, kidneys, smooth muscle lineage and limb skeleton... (Review)
Review
The lateral plate mesoderm (LPM) forms the progenitor cells that constitute the heart and cardiovascular system, blood, kidneys, smooth muscle lineage and limb skeleton in the developing vertebrate embryo. Despite this central role in development and evolution, the LPM remains challenging to study and to delineate, owing to its lineage complexity and lack of a concise genetic definition. Here, we outline the processes that govern LPM specification, organization, its cell fates and the inferred evolutionary trajectories of LPM-derived tissues. Finally, we discuss the development of seemingly disparate organ systems that share a common LPM origin.
Topics: Animals; Cardiovascular System; Cell Differentiation; Cell Lineage; Embryonic Development; Gene Expression Regulation, Developmental; Humans; Mesoderm; Stem Cells; Transcription Factors
PubMed: 32561665
DOI: 10.1242/dev.175059 -
Development (Cambridge, England) Apr 2023During gastrulation, early embryos specify and reorganise the topology of their germ layers. Surprisingly, this fundamental and early process does not appear to be... (Review)
Review
During gastrulation, early embryos specify and reorganise the topology of their germ layers. Surprisingly, this fundamental and early process does not appear to be rigidly constrained by evolutionary pressures; instead, the morphology of gastrulation is highly variable throughout the animal kingdom. Recent experimental results demonstrate that it is possible to generate different alternative gastrulation modes in single organisms, such as in early cnidarian, arthropod and vertebrate embryos. Here, we review the mechanisms that underlie the plasticity of vertebrate gastrulation both when experimentally manipulated and during evolution. Using the insights obtained from these experiments we discuss the effects of the increase in yolk volume on the morphology of gastrulation and provide new insights into two crucial innovations during amniote gastrulation: the transition from a ring-shaped mesoderm domain in anamniotes to a crescent-shaped domain in amniotes, and the evolution of the reptilian blastoporal plate/canal into the avian primitive streak.
Topics: Animals; Gastrulation; Gastrula; Mesoderm; Germ Layers; Primitive Streak
PubMed: 37067451
DOI: 10.1242/dev.200885 -
ELife Jun 2022Advanced imaging techniques reveal details of the interactions between the two layers of the embryonic midgut that influence its ultimate shape.
Advanced imaging techniques reveal details of the interactions between the two layers of the embryonic midgut that influence its ultimate shape.
Topics: Animals; Drosophila; Endoderm; Gene Expression Regulation, Developmental; Mesoderm; Morphogenesis
PubMed: 35771125
DOI: 10.7554/eLife.80416 -
Nature Feb 2024The house mouse (Mus musculus) is an exceptional model system, combining genetic tractability with close evolutionary affinity to humans. Mouse gestation lasts only 3...
The house mouse (Mus musculus) is an exceptional model system, combining genetic tractability with close evolutionary affinity to humans. Mouse gestation lasts only 3 weeks, during which the genome orchestrates the astonishing transformation of a single-cell zygote into a free-living pup composed of more than 500 million cells. Here, to establish a global framework for exploring mammalian development, we applied optimized single-cell combinatorial indexing to profile the transcriptional states of 12.4 million nuclei from 83 embryos, precisely staged at 2- to 6-hour intervals spanning late gastrulation (embryonic day 8) to birth (postnatal day 0). From these data, we annotate hundreds of cell types and explore the ontogenesis of the posterior embryo during somitogenesis and of kidney, mesenchyme, retina and early neurons. We leverage the temporal resolution and sampling depth of these whole-embryo snapshots, together with published data from earlier timepoints, to construct a rooted tree of cell-type relationships that spans the entirety of prenatal development, from zygote to birth. Throughout this tree, we systematically nominate genes encoding transcription factors and other proteins as candidate drivers of the in vivo differentiation of hundreds of cell types. Remarkably, the most marked temporal shifts in cell states are observed within one hour of birth and presumably underlie the massive physiological adaptations that must accompany the successful transition of a mammalian fetus to life outside the womb.
Topics: Animals; Female; Mice; Pregnancy; Animals, Newborn; Cell Differentiation; Embryo, Mammalian; Embryonic Development; Gastrula; Gastrulation; Kidney; Mesoderm; Neurons; Retina; Single-Cell Analysis; Somites; Time Factors; Time-Lapse Imaging; Transcription Factors; Transcription, Genetic; Organ Specificity
PubMed: 38355799
DOI: 10.1038/s41586-024-07069-w