Mouse Models of Gonadotrope Development

Stallings, Caitlin E; Kapali, Jyoti; Ellsworth, Buffy S.

doi:10.1016/bs.pmbts.2016.08.001

Cited by 9 publications

(4 citation statements)

References 211 publications

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“…Strikingly, the neonatal AP also contains gonadotrope progenitor and precursor subclusters as characterized by gradually increasing gonadotrope markers ( Nr5a1 , Cga , Lhb , Fshb , and Gnrhr ) in parallel with declining stem cell factors ( Sox2 , Krt8 , and Sox9 ) ( Figure 1A, B , Figure 1—figure supplement 1B ). The gonadotrope lineage arises last during embryonic development just before birth ( Stallings et al, 2016 ), and some cells in the neonatal AP indeed coexpress SOX2 and the common gonadotropin subunit αGSU ( Figure 1—figure supplement 2C ). In further support of an endocrine progenitor phenotype (as opposed to a stem cell state), DEG analysis revealed upregulation of genes involved in hormone production (e.g., Chga , Ascl1 , Cga , and Insm1 ) and enrichment of GO terms related to endocrine differentiation and secretion when compared to the stem cell clusters ( Figure 1—figure supplement 2C ; Figure 1—figure supplement 2—source data 3 ).…”

Section: Resultsmentioning

confidence: 99%

Decoding the activated stem cell phenotype of the neonatally maturing pituitary

Laporte

Hermans

Vriendt

et al. 2022

eLife

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The pituitary represents the endocrine master regulator. In mouse, the gland undergoes active maturation immediately after birth. Here, we in detail portrayed the stem cell compartment of neonatal pituitary. Single-cell RNA-sequencing pictured an active gland, revealing proliferative stem as well as hormonal (progenitor) cell populations. The stem cell pool displayed a hybrid epithelial/mesenchymal phenotype, characteristic of development-involved tissue stem cells. Organoid culturing recapitulated the stem cells’ phenotype, interestingly also reproducing their paracrine activity. The pituitary stem cell-activating interleukin-6 (IL-6) advanced organoid growth, although the neonatal stem cell compartment was not visibly affected in Il6-/- mice, likely due to cytokine family redundancy. Further transcriptomic analysis exposed a pronounced WNT pathway in the neonatal gland, shown to be involved in stem cell activation and to overlap with the (fetal) human pituitary transcriptome. Following local damage, the neonatal gland efficiently regenerates, despite absence of additional stem cell proliferation, or upregulated IL-6 or WNT expression, all in line with the already high stem cell activation status, thereby exposing striking differences with adult pituitary. Together, our study decodes the stem cell compartment of neonatal pituitary, exposing an activated state in the maturing gland. Understanding stem cell activation is key to potential pituitary regenerative prospects.

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Section: Resultsmentioning

confidence: 99%

Decoding the activated stem cell phenotype of the neonatally maturing pituitary

Laporte

Hermans

Vriendt

et al. 2022

eLife

View full text Add to dashboard Cite

show abstract

“…Strikingly, the neonatal AP also contains gonadotrope progenitor and precursor subclusters as characterized by gradually increasing gonadotrope markers ( Nr5a1, Cga, Lhb, Fshb, Gnrhr ) in parallel with declining stem cell factors ( Sox2, Krt8, Sox9 ) (Figure 1A and B – figure supplement 1B). The gonadotrope lineage arises last during embryonic development just before birth (Stallings et al, 2016), and some cells in the neonatal AP indeed co-express SOX2 and the common gonadotropin subunit αGSU (Figure 1 - figure supplement 1G). In further support of an endocrine progenitor phenotype (as opposed to a stem cell state), DEG analysis revealed upregulation of genes involved in hormone production (e.g.…”

Section: Resultsmentioning

confidence: 99%

Decoding the activated stem cell phenotype of the vividly maturing neonatal pituitary

Laporte

Hermans

Vriendt

et al. 2022

Preprint

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The pituitary represents the endocrine master regulator. In mouse, the gland undergoes vivid maturation immediately after birth. Here, we in detail portrayed the stem cell compartment of neonatal pituitary. Single-cell RNA-sequencing pictured an active gland, revealing proliferative stem as well as hormonal (progenitor) cell populations. The stem cell pool displayed a hybrid epithelial/mesenchymal phenotype, characteristic of development-involved tissue stem cells. Organoid culturing recapitulated the stem cells' phenotype, interestingly also reproducing their paracrine activity. The pituitary stem cell-activating interleukin-6 (IL-6) advanced organoid growth, although the neonatal stem cell compartment was not visibly affected in IL-6-/- mice, possibly due to cytokine family redundancy. Further transcriptomic analysis exposed a pronounced WNT pathway in the neonatal gland, shown to be involved in stem cell activation and to overlap with the (fetal) human pituitary transcriptome. Following local damage, the neonatal gland efficiently regenerates, despite absence of additional stem cell proliferation, or upregulated IL-6 or WNT expression, all in line with the already high stem cell activation status, thereby divulging striking differences with adult pituitary. Together, our study decodes the stem cell compartment of neonatal pituitary, exposing an activated state in the vividly maturing gland. Understanding stem cell activation is key to potential pituitary regenerative prospects.

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“…Musashi may thus be involved indirectly in promoting Lhb mRNA expression by increasing SF-1 and GATA2 levels, which bind to the Lhb gene promoter to promote GnRH responsiveness 74 , 75 . GATA2 is also an important transcription factor for Cga, Lhb, and SF-1/ Nr5a1 gene expression 76 . Our findings support a model in which Musashi acts during the estrous cycle to activate translation of the Gata2 and Nr5a1 mRNAs to provide SF-1 and GATA2 protein to transcriptionally activate the Lhb mRNA to support a midcycle LH surge.…”

Section: Discussionmentioning

confidence: 99%

The Musashi RNA binding proteins direct the translational activation of key pituitary mRNAs

Banik,

Moreira,

Lim

et al. 2024

Sci Rep

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The pituitary functions as a master endocrine gland that secretes hormones critical for regulation of a wide variety of physiological processes including reproduction, growth, metabolism and stress responses. The distinct hormone-producing cell lineages within the pituitary display remarkable levels of cell plasticity that allow remodeling of the relative proportions of each hormone-producing cell population to meet organismal demands. The molecular mechanisms governing pituitary cell plasticity have not been fully elucidated. Our recent studies have implicated a role for the Musashi family of sequence-specific mRNA binding proteins in the control of pituitary hormone production, pituitary responses to hypothalamic stimulation and modulation of pituitary transcription factor expression in response to leptin signaling. To date, these actions of Musashi in the pituitary appear to be mediated through translational repression of the target mRNAs. Here, we report Musashi1 directs the translational activation, rather than repression, of the Prop1, Gata2 and Nr5a1 mRNAs which encode key pituitary lineage specification factors. We observe that Musashi1 further directs the translational activation of the mRNA encoding the glycolipid Neuronatin (Nnat) as determined both in mRNA reporter assays as well as in vivo. Our findings suggest a complex bifunctional role for Musashi1 in the control of pituitary cell function.

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Mouse Models of Gonadotrope Development

Cited by 9 publications

References 211 publications

Decoding the activated stem cell phenotype of the neonatally maturing pituitary

Decoding the activated stem cell phenotype of the neonatally maturing pituitary

Decoding the activated stem cell phenotype of the vividly maturing neonatal pituitary

The Musashi RNA binding proteins direct the translational activation of key pituitary mRNAs

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