Temporal transcriptional profiling of somatic and germ cells reveals biased lineage priming of sexual fate in the fetal mouse gonad

Autor: Steven C. Munger, Samantha A. Jameson, Anirudh Natarajan, Danielle M. Maatouk, Jonah Cool, Blanche Capel, Lindsey Mork, Tony DeFalco
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Male
Cancer Research
Cell type
Gonad
Stromal cell
lcsh:QH426-470
Somatic cell
Cellular differentiation
Embryonic Development
Biology
03 medical and health sciences
Mice
0302 clinical medicine
Model Organisms
Genome Analysis Tools
Genetics
medicine
Morphogenesis
Animals
Cell Lineage
Progenitor cell
Gonads
Molecular Biology
Genetics (clinical)
Ecology
Evolution
Behavior and Systematics
030304 developmental biology
0303 health sciences
Sexual differentiation
Systems Biology
Computational Biology
Endothelial Cells
Gene Expression Regulation
Developmental
Cell Differentiation
Genomics
Animal Models
Sex Determination Processes
Microarray Analysis
lcsh:Genetics
medicine.anatomical_structure
Germ Cells
Female
Stromal Cells
Organism Development
030217 neurology & neurosurgery
Germ cell
Research Article
Developmental Biology
Zdroj: PLoS Genetics, Vol 8, Iss 3, p e1002575 (2012)
PLoS Genetics
ISSN: 1553-7404
1553-7390
Popis: The divergence of distinct cell populations from multipotent progenitors is poorly understood, particularly in vivo. The gonad is an ideal place to study this process, because it originates as a bipotential primordium where multiple distinct lineages acquire sex-specific fates as the organ differentiates as a testis or an ovary. To gain a more detailed understanding of the process of gonadal differentiation at the level of the individual cell populations, we conducted microarrays on sorted cells from XX and XY mouse gonads at three time points spanning the period when the gonadal cells transition from sexually undifferentiated progenitors to their respective sex-specific fates. We analyzed supporting cells, interstitial/stromal cells, germ cells, and endothelial cells. This work identified genes specifically depleted and enriched in each lineage as it underwent sex-specific differentiation. We determined that the sexually undifferentiated germ cell and supporting cell progenitors showed lineage priming. We found that germ cell progenitors were primed with a bias toward the male fate. In contrast, supporting cells were primed with a female bias, indicative of the robust repression program involved in the commitment to XY supporting cell fate. This study provides a molecular explanation reconciling the female default and balanced models of sex determination and represents a rich resource for the field. More importantly, it yields new insights into the mechanisms by which different cell types in a single organ adopt their respective fates.
Author Summary How cells diverge from a common progenitor and adopt specific fates is still poorly understood. We analyzed gene expression profiles in the distinct cell lineages of the gonad over the period when sex determination occurs. The undifferentiated progenitor cells expressed genes characteristic of both sexual fates, explaining the plasticity of the gonadal cells to differentiate as male or female cell types. The establishment of sex-specific fate in both the germ cells and somatic cells involved activation of some genes; but, importantly, we show that an active repression of genes associated with the alternative pathway is also a characteristic of cell fate commitment. Although germ cell progenitors expressed genes associated with both possible fates, genes characteristic of the male fate were over-represented in the progenitors, giving them a male bias. However, in somatic cell progenitors, which control sex determination, genes associated with the female fate were over-represented. These results suggest an explanation for why the female fate is the developmental default for the gonad, and they advance our understanding of how complex transcriptional networks regulate fate determination during organ development.
Databáze: OpenAIRE
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