Transcriptome analysis of healthy adrenal glands, mbryonic neural crest cells, and neuroblastoma
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PROVIDER: PRJNA379263 | ENA |
REPOSITORIES: ENA
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Project description:We addressed heterogeneity of neural crest- and mesoderm-derived lineages developing into adrenal glands, kidneys, endothelium and hematopoietic tissue for understanding transitions, integration and tumor-initiating states between week 6 and 14 of human development. We identified new transitions connecting intermediate mesoderm and progenitors of organ primordia, hematopoietic system and endothelial subtypes. Unexpectedly, we revealed that in humans, contrary to mice, nerve-associated Schwann cell precursors give rise to highly-proliferative sympathoblasts within adrenal gland, which in turn could transit into neuroendocrine chromaffin cells. The analysis of cell state signatures in relation to survival curves of patients suggested Schwann cell precursor-derived sympathoadrenal subtypes as origin for different neuroblastoma tumors.
2021-01-14 | GSE147821 | GEO
Project description:Ectoderm-derived neural crest is a transient structure arising during early embryogenesis in vertebrates. Neural crest consists of four derivatives based on their anterior- to posterior location along the body axis; cranial, vagal, trunk and sacral, respectively. We recently showed that trunk neural crest-specific gene MOXD1 functions as a tumor suppressor in trunk neural crest-derived childhood cancer form neuroblastoma and is essential for proper development of healthy adrenal glands. However, the role of MOXD1 during early embryogenesis is not known. Here, we conditionally knocked out MOXD1 in trunk neural crest cells before they become lineage-committed, using a CRISPR/Cas9 approach in chick embryos. Assessment of embryo growth showed that knockout of MOXD1 delayed development with knockout embryos being smaller. RNA sequencing of trunk-derived neural crest cells from control and knockout embryos showed enrichment of genes connected to gland development, copper ion metabolism and neuroblastoma progression. In conclusion, MOXD1 is important during early and prolonged embryonic development with effects on gland formation, possibly mediated via its role in copper metabolism.
2023-09-13 | GSE242700 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2017-03-15 | GSE96631 | GEO
Project description:Neuroblastoma is a common childhood malignant tumor of neural crest origin with remarkable heterogeneity in outcomes. Amplification of the oncogene MYCN is strongly associated with highly malignant behaviour and poor prognosis. Here, we used human ESC-derived neural crest model to recapitulate the initiation of MYCN-driven neuroblastoma and to identify MYCN downstream effectors. Our results show that induced deregulation of MYCN in human neural crest progenitor cells is sufficient to induce tumors that recapitulate the pathological and molecular features of human MYCN-amplified neuroblastoma(MNA-NB). By using this platform, we are able to identify a group of 28 genes that are associated with MYCN expression level only in MNA-NB.
2021-09-01 | GSE137975 | GEO
Project description:The human adrenal glands are highly dynamic endocrine organs that are involved in the secretion of various hormones such as steroids and catecholamines. Here we present a single-nuclei and spatial transcriptomic analysis of healthy adult human adrenal glands to provide a complete adrenal gland atlas. With this, we show how such an atlas can be taken advantage when studying adrenocortical diseases, such as adrenocortical adenomas (ACA). Using nornal adrenal as reference, we showed a high intra-tumoural heterogeneity in the single-nuclei transcriptome of ACA, revealing the presence of specific cell populations associated with cortisol secretion and genetic background.
2023-01-01 | E-MTAB-12129 | biostudies-arrayexpress
Project description:Human fetal adrenal glands are huge endocrine organ, produce prodigious quantities of dehydroepiandrosterone and its sulfate (DHEA/DHEAS), which is the most prominent precursor for steroid hormones, adrenal gonads dysfunction leads to states of virilization or effemination. However, for a long time the function of fetal adrenal in initial sex differentiation is unclear. Herein, we draw out a single-cell transcriptional landscape of human fetal adrenals and gonad from 6 to 14 gestational weeks (GW). We found that the adrenal glands begin to express CYP17A1 steroid-related enzyme much early than testis, subsequent testis steroid express pattern support de novo or halfway testosterone synthesis. Excepted steroidogenic cell, notably, the immune cells or neurocyte shows steroid metabolism or regulation ability, such as CD5L+ macrophage interacted with steroidogenic cell and SRD5A1+ AKR1C2+ chromaffin cells synthesis active testosterone DHT through backdoor pathway. Sex different were found at adrenal glands and gonad development: there is a small HSD3B2 peak occurs only in female adrenal glands around 10-12 GW within the time window of sex differentiation. SST expression levels or SST+ cells quantity in adrenal glands and gonads are different in two gender. Our research indicates that a sex different in spatial and temporal disparities steroidogenic regulatory networks in adrenal glands and gonads, facilitating further exploration of development and physiology of human adrenal glands.
2022-08-08 | GSE167860 | GEO
Project description:Neuroblastoma is the most common extracranial solid tumor and accounts for ~10% of pediatric cancer-related deaths. The exact cell-of-origin has yet to be elucidated, but it is generally accepted that neuroblastoma derives from the neural crest and should thus be considered an embryonal malignancy. About 50% of primary neuroblastoma tumors arise in the adrenal gland. Here we present an atlas of the developing mouse adrenal gland at a single cell level. Five main cell cluster groups (medulla, cortex, endothelial, stroma and immune) make up the mouse adrenal gland during fetal development. The medulla group, which is of neural crest origin, is further divided into seven clusters. Of interest is the Schwann cell precursor (SCP) and the neuroblast cluster, a highly cycling cluster that shares markers with sympathoblasts. The signature of the medullary SCP cluster differentiates neuroblastoma patients based on disease phenotype: the SCP signature score anti- correlates with ALK and MYCN expression, two indicators of poor prognosis. Furthermore, a high SCP signature score is associated with better overall survival rates. This study provides an insight in the developing adrenal gland and introduces the SCP gene signature as being of interest for further research in understanding neuroblastoma phenotype.
2021-02-01 | GSE162238 | GEO
Project description:Neuroblastoma is an embryonal tumor arising from the neural crest. It can be mimicked in mice by neural crest-specific overepxression of oncogenes such as MYCN or mutated ALK. Expression profiling of murine neuroblastoma driven by MYCN were compared to those driven by mutated ALK and to mouse normal adrenal tissue.
2012-03-31 | E-GEOD-32386 | biostudies-arrayexpress
Project description:Present material was analyzed for activation of intracellular pathways in neuroblastoma compared to normal tissues (neural crest cells, healthy adrenal gland).
2017-03-15 | GSE96629 | GEO
Project description:Neuroblastoma is a pediatric tumor of the developing sympathetic nervous system. However, the cellular origin of neuroblastoma remains to be defined. Here, we study single-cell transcriptomes of neuroblastomas and normal human developing adrenal glands at various stages of embryonic and fetal development. We define normal differentiation trajectories during adrenal medullary development and identify the cellular origin of neuroblastoma. Importantly, adrenergic and mesenchymal neuroblastomas with varying clinical phenotypes match different temporal states along normal differentiation trajectories, with the degree of differentiation corresponding to clinical prognosis.
| EGAS00001004388 | EGA