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Cell May 2022Spatially resolved transcriptomic technologies are promising tools to study complex biological processes such as mammalian embryogenesis. However, the imbalance between...
Spatially resolved transcriptomic technologies are promising tools to study complex biological processes such as mammalian embryogenesis. However, the imbalance between resolution, gene capture, and field of view of current methodologies precludes their systematic application to analyze relatively large and three-dimensional mid- and late-gestation embryos. Here, we combined DNA nanoball (DNB)-patterned arrays and in situ RNA capture to create spatial enhanced resolution omics-sequencing (Stereo-seq). We applied Stereo-seq to generate the mouse organogenesis spatiotemporal transcriptomic atlas (MOSTA), which maps with single-cell resolution and high sensitivity the kinetics and directionality of transcriptional variation during mouse organogenesis. We used this information to gain insight into the molecular basis of spatial cell heterogeneity and cell fate specification in developing tissues such as the dorsal midbrain. Our panoramic atlas will facilitate in-depth investigation of longstanding questions concerning normal and abnormal mammalian development.
Topics: Animals; DNA; Embryo, Mammalian; Female; Gene Expression Profiling; Mammals; Mice; Organogenesis; Pregnancy; Sequence Analysis, RNA; Single-Cell Analysis; Transcriptome
PubMed: 35512705
DOI: 10.1016/j.cell.2022.04.003 -
Wiley Interdisciplinary Reviews.... 2015The signaling component of the mammalian Fibroblast Growth Factor (FGF) family is comprised of eighteen secreted proteins that interact with four signaling tyrosine... (Review)
Review
The signaling component of the mammalian Fibroblast Growth Factor (FGF) family is comprised of eighteen secreted proteins that interact with four signaling tyrosine kinase FGF receptors (FGFRs). Interaction of FGF ligands with their signaling receptors is regulated by protein or proteoglycan cofactors and by extracellular binding proteins. Activated FGFRs phosphorylate specific tyrosine residues that mediate interaction with cytosolic adaptor proteins and the RAS-MAPK, PI3K-AKT, PLCγ, and STAT intracellular signaling pathways. Four structurally related intracellular non-signaling FGFs interact with and regulate the family of voltage gated sodium channels. Members of the FGF family function in the earliest stages of embryonic development and during organogenesis to maintain progenitor cells and mediate their growth, differentiation, survival, and patterning. FGFs also have roles in adult tissues where they mediate metabolic functions, tissue repair, and regeneration, often by reactivating developmental signaling pathways. Consistent with the presence of FGFs in almost all tissues and organs, aberrant activity of the pathway is associated with developmental defects that disrupt organogenesis, impair the response to injury, and result in metabolic disorders, and cancer. For further resources related to this article, please visit the WIREs website.
Topics: Animals; Cell Differentiation; Cell Movement; Cell Proliferation; Embryonic Development; Energy Metabolism; Fibroblast Growth Factors; Homeostasis; Humans; Models, Biological; Organogenesis; Receptors, Fibroblast Growth Factor; Signal Transduction; Voltage-Gated Sodium Channels
PubMed: 25772309
DOI: 10.1002/wdev.176 -
Development (Cambridge, England) Jun 2015The liver is a central regulator of metabolism, and liver failure thus constitutes a major health burden. Understanding how this complex organ develops during... (Review)
Review
The liver is a central regulator of metabolism, and liver failure thus constitutes a major health burden. Understanding how this complex organ develops during embryogenesis will yield insights into how liver regeneration can be promoted and how functional liver replacement tissue can be engineered. Recent studies of animal models have identified key signaling pathways and complex tissue interactions that progressively generate liver progenitor cells, differentiated lineages and functional tissues. In addition, progress in understanding how these cells interact, and how transcriptional and signaling programs precisely coordinate liver development, has begun to elucidate the molecular mechanisms underlying this complexity. Here, we review the lineage relationships, signaling pathways and transcriptional programs that orchestrate hepatogenesis.
Topics: Animals; Cell Differentiation; Cell Lineage; Hepatocytes; Humans; Liver; Liver Diseases; Mice; Organogenesis; Signal Transduction; Stem Cells
PubMed: 26081571
DOI: 10.1242/dev.114215 -
Cell Stem Cell Feb 2021Organoids are powerful models for studying tissue development, physiology, and disease. However, current culture systems disrupt the inductive tissue-tissue interactions...
Organoids are powerful models for studying tissue development, physiology, and disease. However, current culture systems disrupt the inductive tissue-tissue interactions needed for the complex morphogenetic processes of native organogenesis. Here, we show that mouse embryonic stem cells (mESCs) can be coaxed to robustly undergo fundamental steps of early heart organogenesis with an in-vivo-like spatiotemporal fidelity. These axially patterned embryonic organoids (gastruloids) mimic embryonic development and support the generation of cardiovascular progenitors, including first and second heart fields. The cardiac progenitors self-organize into an anterior domain reminiscent of a cardiac crescent before forming a beating cardiac tissue near a putative primitive gut-like tube, from which it is separated by an endocardial-like layer. These findings unveil the surprising morphogenetic potential of mESCs to execute key aspects of organogenesis through the coordinated development of multiple tissues. This platform could be an excellent tool for studying heart development in unprecedented detail and throughput.
Topics: Animals; Embryonic Development; Heart; Mice; Mouse Embryonic Stem Cells; Organogenesis; Organoids
PubMed: 33176168
DOI: 10.1016/j.stem.2020.10.013 -
Cell May 2023The third and fourth weeks of gestation in primates are marked by several developmental milestones, including gastrulation and the formation of organ primordia. However,...
The third and fourth weeks of gestation in primates are marked by several developmental milestones, including gastrulation and the formation of organ primordia. However, our understanding of this period is limited due to restricted access to in vivo embryos. To address this gap, we developed an embedded 3D culture system that allows for the extended ex utero culture of cynomolgus monkey embryos for up to 25 days post-fertilization. Morphological, histological, and single-cell RNA-sequencing analyses demonstrate that ex utero cultured monkey embryos largely recapitulated key events of in vivo development. With this platform, we were able to delineate lineage trajectories and genetic programs involved in neural induction, lateral plate mesoderm differentiation, yolk sac hematopoiesis, primitive gut, and primordial germ-cell-like cell development in monkeys. Our embedded 3D culture system provides a robust and reproducible platform for growing monkey embryos from blastocysts to early organogenesis and studying primate embryogenesis ex utero.
Topics: Animals; Embryo, Mammalian; Macaca fascicularis; Embryonic Development; Blastocyst; Organogenesis; Primates
PubMed: 37172563
DOI: 10.1016/j.cell.2023.04.020 -
Nature Reviews. Molecular Cell Biology Dec 2017Stem cells and their local microenvironment, or niche, communicate through mechanical cues to regulate cell fate and cell behaviour and to guide developmental processes.... (Review)
Review
Stem cells and their local microenvironment, or niche, communicate through mechanical cues to regulate cell fate and cell behaviour and to guide developmental processes. During embryonic development, mechanical forces are involved in patterning and organogenesis. The physical environment of pluripotent stem cells regulates their self-renewal and differentiation. Mechanical and physical cues are also important in adult tissues, where adult stem cells require physical interactions with the extracellular matrix to maintain their potency. In vitro, synthetic models of the stem cell niche can be used to precisely control and manipulate the biophysical and biochemical properties of the stem cell microenvironment and to examine how the mode and magnitude of mechanical cues, such as matrix stiffness or applied forces, direct stem cell differentiation and function. Fundamental insights into the mechanobiology of stem cells also inform the design of artificial niches to support stem cells for regenerative therapies.
Topics: Adult Stem Cells; Animals; Biomechanical Phenomena; Extracellular Matrix; Humans; Organogenesis; Regeneration; Stem Cell Niche
PubMed: 29115301
DOI: 10.1038/nrm.2017.108 -
Cell Stem Cell Apr 2022Advances in self-organizing cardiac organoids to recapitulate human cardiogenesis have provided a powerful tool for unveiling human cardiac development, studying... (Review)
Review
Advances in self-organizing cardiac organoids to recapitulate human cardiogenesis have provided a powerful tool for unveiling human cardiac development, studying cardiovascular diseases, testing drugs, and transplantation. Here, we highlight the recent remarkable progress on multicellular cardiac organoids and review the current status for their practical applications. We then introduce key readouts and tools for assessing cardiac organoids for clinical applications, address major challenges, and provide suggestions for each assessment method. Lastly, we discuss the current limitations of cardiac organoids as miniature models of the human heart and suggest a direction for moving forward toward building the mini-heart from cardiac organoids.
Topics: Cardiovascular Diseases; Heart; Humans; Organogenesis; Organoids
PubMed: 35395186
DOI: 10.1016/j.stem.2022.03.012 -
Neuron Jan 2016The human CNS follows a pattern of development typical of all mammals, but certain neurodevelopmental features are highly derived. Building the human CNS requires the... (Review)
Review
The human CNS follows a pattern of development typical of all mammals, but certain neurodevelopmental features are highly derived. Building the human CNS requires the precise orchestration and coordination of myriad molecular and cellular processes across a staggering array of cell types and over a long period of time. Dysregulation of these processes affects the structure and function of the CNS and can lead to neurological or psychiatric disorders. Recent technological advances and increased focus on human neurodevelopment have enabled a more comprehensive characterization of the human CNS and its development in both health and disease. The aim of this review is to highlight recent advancements in our understanding of the molecular and cellular landscapes of the developing human CNS, with focus on the cerebral neocortex, and the insights these findings provide into human neural evolution, function, and dysfunction.
Topics: Animals; Brain; Central Nervous System; Humans; Neurodevelopmental Disorders; Neurogenesis; Organogenesis
PubMed: 26796689
DOI: 10.1016/j.neuron.2015.12.008 -
Development (Cambridge, England) Jun 2022Prostate organogenesis begins during embryonic development and continues through puberty when the prostate becomes an important exocrine gland of the male reproductive...
Prostate organogenesis begins during embryonic development and continues through puberty when the prostate becomes an important exocrine gland of the male reproductive system. The specification and growth of the prostate is regulated by androgens and is largely a result of cell-cell communication between the epithelium and mesenchyme. The fields of developmental and cancer biology have long been interested in prostate organogenesis because of its relevance for understanding prostate diseases, and research has expanded in recent years with the advent of novel technologies, including genetic-lineage tracing, single-cell RNA sequencing and organoid culture methods, that have provided important insights into androgen regulation, epithelial cell origins and cellular heterogeneity. We discuss these findings, putting them into context with what is currently known about prostate organogenesis.
Topics: Androgens; Epithelial Cells; Epithelium; Humans; Male; Mesoderm; Organogenesis; Prostate
PubMed: 35726824
DOI: 10.1242/dev.200394 -
Cell Stem Cell Oct 2021During embryogenesis, optic vesicles develop from the diencephalon via a multistep process of organogenesis. Using induced pluripotent stem cell (iPSC)-derived human...
During embryogenesis, optic vesicles develop from the diencephalon via a multistep process of organogenesis. Using induced pluripotent stem cell (iPSC)-derived human brain organoids, we attempted to simplify the complexities and demonstrate formation of forebrain-associated bilateral optic vesicles, cellular diversity, and functionality. Around day 30, brain organoids attempt to assemble optic vesicles, which develop progressively as visible structures within 60 days. These optic vesicle-containing brain organoids (OVB-organoids) constitute a developing optic vesicle's cellular components, including primitive corneal epithelial and lens-like cells, retinal pigment epithelia, retinal progenitor cells, axon-like projections, and electrically active neuronal networks. OVB-organoids also display synapsin-1, CTIP-positive myelinated cortical neurons, and microglia. Interestingly, various light intensities could trigger photosensitive activity of OVB-organoids, and light sensitivities could be reset after transient photobleaching. Thus, brain organoids have the intrinsic ability to self-organize forebrain-associated primitive sensory structures in a topographically restricted manner and can allow interorgan interaction studies within a single organoid.
Topics: Cell Differentiation; Embryonic Development; Humans; Induced Pluripotent Stem Cells; Organogenesis; Organoids; Prosencephalon
PubMed: 34407456
DOI: 10.1016/j.stem.2021.07.010