Single-cell transcriptional diversity is a hallmark of developmental potential
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ABSTRACT:
PROVIDER: PRJNA576262 | ENA |
REPOSITORIES: ENA
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Project description:Single-cell RNA sequencing (scRNA-seq) is a powerful approach for reconstructing cellular differentiation trajectories. However, inferring both the state and direction of differentiation is challenging. Here, we demonstrate a simple, yet robust, determinant of developmental potential—the number of expressed genes per cell—and leverage this measure of transcriptional diversity to develop a computational framework (CytoTRACE) for predicting differentiation states from scRNA-seq data. When applied to diverse tissue types and organisms, CytoTRACE outperformed previous methods and nearly 19,000 annotated gene sets for resolving 52 experimentally determined developmental trajectories. Additionally, it facilitated the identification of quiescent stem cells and revealed genes that contribute to breast tumorigenesis. This study thus establishes a key RNA-based feature of developmental potential and a platform for delineation of cellular hierarchies (https://cytotrace.stanford.edu).
2020-01-28 | GSE138536 | GEO
Project description:Single-cell RNA sequencing (scRNA-seq) is a powerful approach for reconstructing cellular differentiation trajectories. However, inferring both the state and direction of differentiation is challenging. Here, we demonstrate a simple, yet robust, determinant of developmental potential-the number of expressed genes per cell-and leverage this measure of transcriptional diversity to develop a computational framework (CytoTRACE) for predicting differentiation states from scRNA-seq data. When applied to diverse tissue types and organisms, CytoTRACE outperformed previous methods and nearly 19,000 annotated gene sets for resolving 52 experimentally determined developmental trajectories. Additionally, it facilitated the identification of quiescent stem cells and revealed genes that contribute to breast tumorigenesis. This study thus establishes a key RNA-based feature of developmental potential and a platform for delineation of cellular hierarchies.
| S-EPMC7694873 | biostudies-literature
Project description:Post-transcriptional regulation in cranial neural crest cells expands developmental potential
| PRJNA892136 | ENA
Project description:Post-transcriptional regulation in cranial neural crest cells expands developmental potential [I]
| PRJNA891631 | ENA
Project description:Post-transcriptional regulation in cranial neural crest cells expands developmental potential [II]
| PRJNA892142 | ENA
Project description:GABAergic interneurons are key regulators of cortical circuit function. Among the dozens of reported transcriptionally distinct subtypes of cortical interneurons, neurogliaform cells (NGC) are unique: are recruited by long-range excitatory inputs and the primary source of slow cortical inhibition. Despite their functional importance, the developmental emergence and cellular diversity of NGCs remains unclear. Here, combining single-cell transcriptomics, genetic fate-mapping, electrophysiological morphological characterization, we reveal that discrete molecular subtypes of NGCs, with distinctive functional and anatomic profiles, populate the neocortex. Furthermore, we show that NGC subtypes emerge gradually through development, as incipient differential molecular signatures are apparent in Preoptic Area (POA) born NGC precursors. By identifying NGC developmentally-conserved transcriptional programs, we report that the transcription factor Tox2 constitutes an identity hallmark across NGC subtypes. Using CRISPR-Cas9-mediated genetic loss-of-function, we show that Tox2 is critical for NGC development: POA-born cells lacking Tox2 fail to differentiate into NGCs. Together, these results reveal that NGCs are born from a spatially restricted pool of Tox2+ POA precursors, after which intra-type diverging molecular programs are gradually acquired post-mitotically and result in functionally and molecularly discrete NGC cortical subtypes.
2023-06-30 | GSE225639 | GEO
Project description:Transcriptional disorganization of fibroblasts is a hallmark of the aging heart
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Project description:Developmental emergence of cortical neurogliaform cell diversity
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Project description:Purpose: To define the cone photoreceptor diversity and underlying transcriptional controls in mouse retina Methods: Individual retinal cone cells were isolated by micro-manipulator from dissociated pieces of superior/inferior retina from heterozygous (or homozygous) Thrb-b2Cre:Ai6 mice. Single cell libraries were constructed for RNA-seq analysis. Thrb-b2Cre;Rosa26-Sun1Gfp mice were used to isolate cone nuclei for ATAC-seq analysis. Thrb-HAB mice were used to identify TRb2 genomic binding sites using ChAP-seq analysis. Results: Developmental analyses of individual cones revealed a network of gradient genes. Many of these gradient genes are regulated by TRb2, a thyroid hormone receptor that has been associated with color visual impairment. Conclusions: The results suggest that TRb2 controls chromatin remodeling and transcriptional plasticity in the cone lineage to promote diversity.
2022-12-05 | GSE203481 | GEO
Project description:Developmental potential is progressively restricted after germ layer specification during gastrulation. However, cranial neural crest cells challenge this paradigm, as they develop from anterior ectoderm yet give rise to both mesodermal derivatives of the craniofacial skeleton and ectodermal derivatives of the peripheral nervous system. How cranial neural crest cells differentiate into multiple lineages is poorly understood. Here, we demonstrate that cranial neural crest cells possess a transient state of increased chromatin accessibility; and that the earliest premigratory neural crest are biased towards either a neuronal or ectomesenchymal fate, with each lineage expressing distinct factors from the pluripotent state. We profile the spatiotemporal emergence of each neural crest population and demonstrate that the ectomesenchymal lineage forms prior to the neuronal progenitors. Expression of the pluripotency microRNA family miR-302 is maintained in cranial neural crest cells and genetic deletion leads to precocious specification of the ectomesenchymal lineage. We find that miR-302 directly targets Sox9 to slow the timing of ectomesenchyme induction and regulates multiple genes involved in chromatin condensation to maintain accessibility for neuronal differentiation. Loss of mir-302 results in reduced chromatin accessibility in the neuronal progenitor lineage of neural crest and a reduction in peripheral neuron differentiation. Our findings reveal a post-transcriptional mechanism governed by miRNAs from pluripotency as an important mechanism to expand developmental potential of cranial neural crest.
2022-10-25 | GSE216136 | GEO