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Sex hormones control muscle stem cells

ABSTRACT: Sex hormones control muscle stem cells

PROVIDER: PRJNA495363 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7985790_1.fastq.gz	Fastqsanger.gz
	SRR7985790_2.fastq.gz	Fastqsanger.gz
	SRR7985791_1.fastq.gz	Fastqsanger.gz
	SRR7985791_2.fastq.gz	Fastqsanger.gz

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Sex hormones control muscle stem cells

Project description:Quiescent adult muscle stem cells (MuSCs) regenerate skeletal muscle upon injury throughout life. However, aged skeletal muscles fail to maintain stem cell quiescence, leading to declines in MuSC number and functionality. Although autophagy plays an important role in the maintenance of MuSC quiescence, how quiescent MuSCs and their autophagy levels are maintained throughout life is largely unknown. The current study reveals how GnRH, a hypothalamic hormone, maintains the quiescence of adult MuSCs by preventing the onset of senescence and how the decline of sex steroids in organismal ageing is implicated in MuSC ageing.

2019-10-05 | GSE121016 | GEO

Sex hormones establish a reserve pool of adult muscle stem cells at puberty

Project description:Quiescent satellite cells, also known as adult muscle stem cells, possess a remarkable ability to regenerate skeletal muscle upon injury throughout life. Although they mainly originate from multipotent stem/progenitors of the somite, the mechanism underlying the establishment of quiescent satellite cell populations is unknown. Here, we show that sex hormones induce Mind bomb-1 (Mib1) expression in myofibers at puberty, which activates Notch signaling in cycling juvenile satellite cells and causes them to be converted into quiescent adult satellite cells. Myofibers lacking Mib1 failed to send Notch signals to juvenile satellite cells, leading to impaired cell cycle exit and depletion. Genetic and inhibitor studies revealed that the hypothalamic-pituitary-gonadal axis drives Mib1 expression in the myofiber niche. Our data show how sex hormones establish quiescent adult satellite cell populations by regulating the myofiber niche at puberty. Microarray analysis of Veh or DHT-injected 10-day-old mice s.c. injected with Veh or DHT. TA muscles were isolated 24 h after the injection.

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Sex hormones establish a reserve pool of adult muscle stem cells at puberty

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Sex hormones have pervasive effects on thymic epithelial cells

Project description:The goal of our study was to evaluate at the systems-level, the effect of sex hormones on thymic epithelial cells (TECs). To this end, we sequenced the transcriptome of cortical and medullary TECs (cTECs and mTECs) from three groups of 6 month-old mice: males, females and males castrated at four weeks of age. In parallel, we analyzed variations in the size of TEC subsets in those three groups between 1 and 12 months of age. We report that sex hormones have pervasive effects on the transcriptome of TECs: the number of differentially expressed genes was 1,440 in cTECs and 1,783 in mTECs. Sexual dimorphism was particularly conspicuous in cTECs. Male cTECs displayed low proliferation rates that correlated with low expression of Foxn1 and its main targets. Furthermore, male cTECs expressed relatively low levels of genes instrumental in thymocyte expansion (e.g., Dll4) and positive selection (Psmb11 and Ctsl). Nevertheless, cTECs were more abundant in males than females. Accumulation of cTECs in males correlated with differential expression of genes regulating cell survival and cell differentiation. Unexpectedly, we observed that female and male sex hormones repressed promiscuous gene expression in mTECs. Since sex hormones did not affect the expression of Aire per se, they must impinge on the activity of unidentified regulator(s) of promiscuous gene expression in mTECs. The sexual dimorphism of TECs highlighted here may be mechanistically linked to the well-recognized sex differences in susceptibility to infections and autoimmune diseases.

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Identification of sex steroid hormones binding proteins in Pseudomonas aeruginosa.

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Project description:Human embryonic stem cell-derived thyroid follicles were exposed for 3 days to a mixture of the sex hormones beta-estradiol (E2), 5-alpha-dihydrotestosterone (DHT) and progesterone (PG) that resemble the serum levels of human male and female (post-ovulation) of reproductive age. Afterwards, they were exposed for 1 day to the mixtures of sex hormones + 10 uM benzo[a]pyrene (BaP) or 10 uM PCB153. At the end of the treatment period, organoids were dissociated into single cell suspension and single cell RNA-Sequencing (scRNA-Seq) performed.

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Project description:Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are a valuable cell type for studying human cardiac health and disease in vitro. However, it is not known whether hiPSC-CM display sex dimorphism and therefore whether sex should be incorporated as a biological variable in in vitro studies that include this cell type. To date, the vast majority of studies that utilize hiPSC-CM do not include both male and female sex nor stratify results based on sex because it is challenging to amass such a cohort of cells. Here we generated three female and three male hiPSC-lines from adult left ventricular cardiac fibroblasts as a resource for studying sex differences in in vitro cardiac models. We used this resource to generate hiPSC-CM and maintained them in basal media without exogenous hormones. Functional assessment of CM showed enhanced calcium handling in female-derived hiPSC-CM relative to male. Bulk RNA sequencing revealed over 300 differentially expressed genes (DEG) between male and female hiPSC-CM. Gene ontology analysis of DEG showed distinct differences in pathways related to cardiac pathology including cell-cell adhesion, metabolic processes, and response to ischemic stress. Differential expression of the sodium channel auxiliary unit SCN3B was found and validated through patch-clamp measurements of sodium currents showing increased peak amplitude and window current in female hiPSC-CM. These findings highlight the importance of considering sex as a variable when conducting studies to evaluate aspects of human cardiac health and disease related to cardiomyocyte function.

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Healthy human induced pluripotent stem cell-derived cardiomyocytes exhibit sex dimorphism even without the addition of hormones

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