Two parallel neural ectoderm populations contribute to the developing brain [ATAC-seq]
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ABSTRACT:
PROVIDER: PRJNA1207994 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR31934553_1.fastq.gz | Fastqsanger.gz | |||
| SRR31934553_2.fastq.gz | Fastqsanger.gz | |||
| SRR31934554_1.fastq.gz | Fastqsanger.gz | |||
| SRR31934554_2.fastq.gz | Fastqsanger.gz | |||
| SRR31934555_1.fastq.gz | Fastqsanger.gz |
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Project description:Stem cell research strives to create diverse types of human brain cells. Given plentiful successes in converting human pluripotent stem cells (hPSCs) into forebrain and midbrain cells, here we focus on generating cells of the human hindbrain, a life-sustaining brain region. This is, in turn, predicated on a developmental roadmap of when and how brain progenitors diversify from one another. In one model, a common brain progenitor can generate all brain regions. Here our studies of mouse embryos and hPSCs support a different model that as early as gastrulation, two parallel brain progenitors emerge simultaneously: anterior neural ectoderm (forebrain/midbrain progenitor) and posterior neural ectoderm (which forms most of the hindbrain). Expanding on classical studies, we suggest anterior and posterior neural ectoderm are already lineage-committed in vitro and cannot transdifferentiate. Anterior and posterior neural ectoderm have divergent chromatin landscapes, respectively foreshadowing their forebrain versus hindbrain potentials. We differentiated hPSCs into posterior neural ectoderm, and subsequently, hindbrain rhombomere 5/6-specific motor neurons. Anterior and posterior neural ectoderm thus represent two parallel developmental routes to generate forebrain/midbrain vs. hindbrain neurons. Finally, anterior and posterior ectoderm are likely conserved from vertebrates to hemichordates, intimating an ancient neural lineage bifurcation that predated chordates, with implications for nervous system evolution.
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Project description:Stem cell research strives to create diverse types of human brain cells. Given plentiful successes in converting human pluripotent stem cells (hPSCs) into forebrain and midbrain cells, here we focus on generating cells of the human hindbrain, a life-sustaining brain region. This is, in turn, predicated on a developmental roadmap of when and how brain progenitors diversify from one another. In one model, a common brain progenitor can generate all brain regions. Here our studies of mouse embryos and hPSCs support a different model that as early as gastrulation, two parallel brain progenitors emerge simultaneously: anterior neural ectoderm (forebrain/midbrain progenitor) and posterior neural ectoderm (which forms most of the hindbrain). Expanding on classical studies, we suggest anterior and posterior neural ectoderm are already lineage-committed in vitro and cannot transdifferentiate. Anterior and posterior neural ectoderm have divergent chromatin landscapes, respectively foreshadowing their forebrain versus hindbrain potentials. We differentiated hPSCs into posterior neural ectoderm, and subsequently, hindbrain rhombomere 5/6-specific motor neurons. Anterior and posterior neural ectoderm thus represent two parallel developmental routes to generate forebrain/midbrain vs. hindbrain neurons. Finally, anterior and posterior ectoderm are likely conserved from vertebrates to hemichordates, intimating an ancient neural lineage bifurcation that predated chordates, with implications for nervous system evolution.
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Project description:During vertebrate neurulation, the embryonic ectoderm is patterned into lineage progenitors for neural plate, neural crest, placodes and epidermis. Here, we use Xenopus laevis embryos to analyze the spatial and temporal transcriptome of distinct ectodermal domains in the course of neurulation, during the establishment of cell lineages. In order to define the transcriptome of small groups of cells from a single germ layer, and to retain spatial information, dorsal and ventral ectoderm was subdivided along the anterior-posterior and medial-lateral axes by microdissections. Principal Component Analysis on the transcriptomes of these ectoderm fragments primarily identifies embryonic axes and temporal dynamics. This provides a genetic code to define positional information of any ectoderm sample along the anterior-posterior and dorsal-ventral axes, directly from its transcriptome. In parallel, we use Non-Negative Matrix Factorization to predict enhanced gene expression maps onto early and mid-neurula embryos, and specific signatures for each ectoderm area. The clustering of spatial and temporal datasets allowed detection of multiple biologically relevant groups (e.g. Wnt signaling, neural crest development, sensory placode specification, ciliogenesis, germ layer specification). We provide an interactive network interface, EctoMap, for exploring synexpression relationships among genes expressed in the neurula, and suggest several strategies to use this comprehensive dataset to address questions in developmental biology as well as stem cell or cancer research.
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