Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Single-cell transcriptomics of neonatal mouse anterior pituitary in steady-state conditions and after transgenically inflicted local damage

ABSTRACT: The mouse pituitary gland undergoes vivid maturation immediately after birth. During this process, the local stem cell compartment shows signs of activation including elevated abundance and expression of stemness pathways when compared to adult pituitary stem cells. In addition, we found that the neonatal pituitary displays high regeneration efficiency, as occurring following diphtheria toxin (DT)-triggered endocrine cell-ablation injury using the GHCre/iDTR mouse model (expressing Cre recombinase under control of the growth hormone (Gh) promoter, as well as Cre-inducible (floxed) DT receptor (iDTR)). This regeneration is more pronounced than in older mice, which is in line with the activated (stem cell) nature of the neonatal gland. However, it is not known what molecular mechanisms underlie the stem cell activation status in the neonatal gland. Here, we set out to decode the stem cells’ phenotype during the neonatal pituitary maturation stage starting from single cell RNA-sequencing (scRNA-seq) interrogations of neonatal (postnatal day 7, PD7) normal (undamaged) and damaged pituitary (more specifically, its major endocrine anterior lobe).

INSTRUMENT(S): Illumina NovaSeq 6000

ORGANISM(S): Mus musculus

SUBMITTER: Florian Hermans

PROVIDER: E-MTAB-11337 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:In mammals, imprinted genes regulate many critical endocrine processes such as growth, the onset of puberty and maternal reproductive behaviour. Human imprinting disorders (IDs) are caused by genetic and epigenetic mechanisms that alter the expression dosage of imprinted genes. Due to improvements in diagnosis, increasing numbers of patients with IDs are now identified and monitored across their lifetimes. Seminal work has revealed that IDs have a strong endocrine component, yet the contribution of imprinted gene products in the develop-ment and function of the hypothalamo-pituitary axis are not well defined. Postnatal endocrine processes are dependent upon the production of hormones from the pituitary gland. While the actions of a few imprinted genes in pituitary development and function have been described, to date there has been no attempt to link the expression of these genes as a class to the formation and function of this essential organ. This is important because IDs show considerable overlap, and imprinted genes are known to define a transcriptional network related to organ growth. This knowledge deficit is partly due to technical difficulties in obtaining useful transcriptomic data from the pituitary gland, namely, its small size during development and cellular complex-ity in maturity. Here we utilise high-sensitivity RNA sequencing at the embryonic stages, and single-cell RNA sequencing data to describe the imprinted transcriptome of the pituitary gland. In concert, we provide a comprehensive literature review of the current knowledge of the role of imprinted genes in pituitary hormonal pathways and how these relate to IDs. We present new data that implicate imprinted gene networks in the development of the gland and in the stem cell compartment. Furthermore, we suggest novel roles for individual imprinted genes in the aetiology of IDs. Finally, we describe the dynamic regulation of imprinted genes in the pituitary gland of the pregnant mother, with implications for the regulation of maternal metabolic adap-tations to pregnancy.

Dataset Information

Single-cell transcriptomics of neonatal mouse anterior pituitary in steady-state conditions and after transgenically inflicted local damage

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