Design logic of hypothalamus development mapped by single-cell RNA-seq
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ABSTRACT:
PROVIDER: PRJNA548917 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9303100.fastq.gz | Fastqsanger.gz | |||
| SRR9303110.fastq.gz | Fastqsanger.gz | |||
| SRR9303101.fastq.gz | Fastqsanger.gz | |||
| SRR9303102.fastq.gz | Fastqsanger.gz | |||
| SRR9303103.fastq.gz | Fastqsanger.gz |
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Project description:Purpose: We aimed to reconstruct the development formation of cellular identities' heterogeneity in the hypothalamus with single-cell RNA sequencing. We planned to track branching process of neurogenesis and follow the formation of cell identities. Results: We integrate single-cell RNA-seq data on 51,199 cells of ectodermal origin, representing critical stages of pre- and postnatal hypothalamus development, supported by anatomical lineage reconstruction to show that bulk neurogenesis in the hypothalamus, dominated by Notch signalling and its interaction with Ascl1, persists until the neonatal period to produce molecularly distinct astrocytes, ependyma, tanycytes and 30 protoclusters of neurons. Alike in adults, the assignment of neurotransmitters and neuropeptides together with transcription factors as positional marks for each neuronal cluster is sufficient to establish the spatially-resolved taxonomy of hypothalamic neurons. By deducing gene regulatory networks, exemplified by hierarchical gene clusters driven by Onecut2/Onecut3 transcription factors for dopamine neurons, we resolve how neuronal lineages diverge into functionally non-overlapping endocrine subtypes. Dopamine neurons are used to illustrate molecular convergence with their shared neurotransmitter identity representing a mismatch to their molecular distances on multidimensional vector spaces. We demonstrate the existence of non-canonical chemotropic axes in the hypothalamus, particularly sequential ligand-receptor switching in the unexpectedly abundant Slit/Robo cassette. Slit2 is identified in ventricular ependymocytes and implicated in repulsing new-born neurons that sequentially express Robo1 and Robo2 receptors for migration and differentiation. Conclusions: Overall, our unbiased map of hypothalamic cell types and extracellular guidance cues uncovers molecular principles shaping the developmental architecture of the mammalian hypothalamus and rationalise how hypothalamic neuronal heterogeneity is transformed into a multimodal neural unit that retains a virtually infinite adaptive potential throughout life.
2020-05-06 | GSE132730 | GEO
Project description:Molecular and cellular design of ovotestis development
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Project description:Molecular and spatial design of human cerebellar development
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Project description:To determine the global changes in hypothalamic gene expression that may occur at the time of female puberty in this species, animals were euthanized at three different stages, juvenile (25-days of age), early puberty (30-35 days of age) and on the day of the first proestrus (32-37 days of age). According to criteria previously established (Ojeda,S.R.; Urbanski,H.F. Puberty in the rat pp.363-409. The Physiology of Reproduction, 2nd Edition, Vol 2. Edited by Knobil,E.; Neill,J.D. Raven Press, 1994), 25-day-old animals are in the mid- juvenile phase of prepubertal development (JUV). At this time, the vagina is not yet patent and the uterine weight is 60Â mg or less, with no accumulation of intrauterine fluid. Older rats showing a closed vagina, accumulation of intrauterine fluid and an uterine weight less that 180 mg are considered to be in the early proestrous (EP) phase of puberty. Finally, rats still exhibiting a closed vagina, but showing a uterus ballooned with fluid and a uterine weight of at least 200Â mg are considered to be in late proestrus (LP), i.e., the phase of puberty when the first preovulatory surge of LHRH and gonadotropins takes place. The first ovulation occurs the following day. All animals were sacrificed between 1600-1700 h, and the medial basal hypothalamus (MBH) was immediately dissected, as previously described (Rogers,L.C.; Junier,M-P.; Farmer,S.R.; Ojeda,S.R. A sex-related difference in the developmental expression of class II -tubulin messenger RNA in rat hypothalamus. Mol.Cell.Neurosci., 2: 130-138, 1991) and stored in RNAlater according to manufacturerâs instructions. Experiment Overall Design: Affymetrix arrays were used to detect global changes in gene expression in the hypothalamus of normal sexual development of the female rat.
2008-06-16 | E-GEOD-8310 | biostudies-arrayexpress
Project description:Core regularity transcription factors (CR TFs) define cell identity and lineage through an exquisitely precise and logical order during embryogenesis and development. These CR TFs regulated one another in three-dimensional space via distal enhancers that serve as logic gates embedded in their TF recognition sequences. Aberrant chromatin organization resulting in miswired circuitry of enhancer logic is a newly recognized feature in many cancers. Here, we report that PAX3-FOXO1 expression is driven by a translocated FOXO1 distal super enhancer (SE). ChIP-seq in tumors bearing rare PAX translocations implicate enhancer miswiring is a pervasive feature across all FP-RMS tumors. Therefore, our data reveal a mechanism of a translocated hijacked enhancer which disrupts the normal CR TF logic during skeletal muscle development (PAX3 to MYOD to MYOG), replacing it with an infinite loop logic that makes rhabdomyosarcoma cells unable to exit the undifferentiated proliferating stage.
2019-12-25 | GSE136799 | GEO
Project description:A wealth of specialized neuroendocrine command systems intercalated within the hypothalamus control the most fundamental physiological needs in vertebrates1,2. Nevertheless, we lack a developmental blueprint that integrates the molecular determinants of neuronal and glial diversity along temporal and spatial scales of hypothalamus development3. Here we combine single-cell RNA sequencing of 51,199 mouse cells of ectodermal origin, gene regulatory network (GRN) screens in conjunction with genome-wide association study-based disease phenotyping, and genetic lineage reconstruction to show that nine glial and thirty-three neuronal subtypes are generated by mid-gestation under the control of distinct GRNs. Combinatorial molecular codes that arise from neurotransmitters, neuropeptides and transcription factors are minimally required to decode the taxonomical hierarchy of hypothalamic neurons. The differentiation of γ-aminobutyric acid (GABA) and dopamine neurons, but not glutamate neurons, relies on quasi-stable intermediate states, with a pool of GABA progenitors giving rise to dopamine cells4. We found an unexpected abundance of chemotropic proliferation and guidance cues that are commonly implicated in dorsal (cortical) patterning5 in the hypothalamus. In particular, loss of SLIT-ROBO signalling impaired both the production and positioning of periventricular dopamine neurons. Overall, we identify molecular principles that shape the developmental architecture of the hypothalamus and show how neuronal heterogeneity is transformed into a multimodal neural unit to provide virtually infinite adaptive potential throughout life.
| S-EPMC7292733 | biostudies-literature
Project description:Spatially mapped single-cell chromatin accessibility
| PRJNA692203 | ENA
Project description:Pulsed SILAC approaches allow measurement of protein dynamics, including protein translation and degradation. However, its use in quantifying acute changes has been limited due the low labeled peptide stoichiometry. Here, we describe the use of instrument logic to select peaks of interest via targeted mass differences (TMD) for overcoming this limitation. Comparing peptides artificially mixed at low heavy-to-light stoichiometry measured using standard data dependent acquisition with or without TMD revealed 2-3 fold increases in identification without significant loss in quantification precision for both MS2 and MS3 methods. Our benchmarked method approach increases throughput by reducing the necessary machine time. We anticipate that all pulsed SILAC measurements, if combined with TMT or not, would greatly benefit from instrument logic based approaches.
2020-05-29 | PXD018445 | Pride