SOX9 regulates expression of the male fertility gene Ets variant factor 5 ( ETV5 ) during mammalian sex development

Alankarage, Dimuthu; Lavery, Rowena; Svingen, Terje; Kelly, Sabine; Ludbrook, Louisa Mabel; Bagheri‐Fam, Stefan; Koopman, Peter; Harley, Vincent R.

doi:10.1016/j.biocel.2016.08.005

Cited by 14 publications

(10 citation statements)

References 53 publications

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“…Interestingly, two genes defining the AEC2 cell fate, ETV5 and SOX9 , are also expressed in the IPF Lyso pos population, but while SOX9 is expressed at levels exceeding that of bona fide AEC2s, ETV5 expression is much lower, suggesting that they regulate different aspects of the IPF alveolar epithelial fate. Indeed, SOX9 is crucial for mouse and human distal lung epithelium specification [ 53 , 54 , 55 , 56 ], while ETV5 , acting downstream of SOX9 [ 56 , 57 , 58 , 59 ] and FGF signaling [ 60 , 61 ], is crucial for AEC2 fate maintenance and is downregulated in transitional states, such as the AEC2 to AEC1 transition [ 61 ]. Interestingly, a recent paper identified a population with similar characteristics in the mouse lung [ 62 ].…”

Section: Discussionmentioning

confidence: 99%

Differential LysoTracker Uptake Defines Two Populations of Distal Epithelial Cells in Idiopathic Pulmonary Fibrosis

Wasnick

Shalashova

Wilhelm

et al. 2022

Cells

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Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal degenerative lung disease of unknown etiology. Although in its final stages it implicates, in a reactive manner, all lung cell types, the initial damage involves the alveolar epithelial compartment, in particular the alveolar epithelial type 2 cells (AEC2s). AEC2s serve dual progenitor and surfactant secreting functions, both of which are deeply impacted in IPF. Thus, we hypothesize that the size of the surfactant processing compartment, as measured by LysoTracker incorporation, allows the identification of different epithelial states in the IPF lung. Flow cytometry analysis of epithelial LysoTracker incorporation delineates two populations (Lysohigh and Lysolow) of AEC2s that behave in a compensatory manner during bleomycin injury and in the donor/IPF lung. Employing flow cytometry and transcriptomic analysis of cells isolated from donor and IPF lungs, we demonstrate that the Lysohigh population expresses all classical AEC2 markers and is drastically diminished in IPF. The Lysolow population, which is increased in proportion in IPF, co-expressed AEC2 and basal cell markers, resembling the phenotype of the previously identified intermediate AEC2 population in the IPF lung. In that regard, we provide an in-depth flow-cytometry characterization of LysoTracker uptake, HTII-280, proSP-C, mature SP-B, NGFR, KRT5, and CD24 expression in human lung epithelial cells. Combining functional analysis with extracellular and intracellular marker expression and transcriptomic analysis, we advance the current understanding of epithelial cell behavior and fate in lung fibrosis.

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Section: Discussionmentioning

confidence: 99%

Differential LysoTracker Uptake Defines Two Populations of Distal Epithelial Cells in Idiopathic Pulmonary Fibrosis

Wasnick

Shalashova

Wilhelm

et al. 2022

Cells

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“…Sox9 targets Etv5 , which is expressed by Sertoli cells and play a role in maintaining the spermatogonial stem cell niche in fetal mice testis, but not in fetal ovary 57 , 58 . In neonatal mice Etv5 is also expressed in germ cells and is essential for spermatogonial proliferation 58 .…”

Section: Discussionmentioning

confidence: 99%

Temporal expression pattern of genes during the period of sex differentiation in human embryonic gonads

Mamsen

Ernst

Borup

et al. 2017

Sci Rep

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The precise timing and sequence of changes in expression of key genes and proteins during human sex-differentiation and onset of steroidogenesis was evaluated by whole-genome expression in 67 first trimester human embryonic and fetal ovaries and testis and confirmed by qPCR and immunohistochemistry (IHC). SRY/SOX9 expression initiated in testis around day 40 pc, followed by initiation of AMH and steroidogenic genes required for androgen production at day 53 pc. In ovaries, gene expression of RSPO1, LIN28, FOXL2, WNT2B, and ETV5, were significantly higher than in testis, whereas GLI1 was significantly higher in testis than ovaries. Gene expression was confirmed by IHC for GAGE, SOX9, AMH, CYP17A1, LIN28, WNT2B, ETV5 and GLI1. Gene expression was not associated with the maternal smoking habits. Collectively, a precise temporal determination of changes in expression of key genes involved in human sex-differentiation is defined, with identification of new genes of potential importance.

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“…(Reichert et al ., 2013a) It is conceivable that tissue and context specific mechanisms may function for the converse to occur, namely that Sox9 may regulate Etv5, which we did not test. For example, Sox9 may regulate Etv5 in the regulation of male fertility, (Alankarage et al ., 2016) kidney development although biochemical evidence is lacking, (Reginensi et al ., 2011) and chondrosarcoma cells based upon functional transfection studies with indirect regulation by miR-145. (Mak et al ., 2015) Elucidating these context-specific mechanisms in pancreatic ductal cells, pancreatitis, and PanIN remain an area of active interest and investigation.…”

Section: Discussionmentioning

confidence: 99%

ETV5 regulates ductal morphogenesis with Sox9 and is critical for regeneration from pancreatitis

Das

Heeg

Pitarresi

et al. 2018

Developmental Dynamics

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SOX9 regulates expression of the male fertility gene Ets variant factor 5 ( ETV5 ) during mammalian sex development

Cited by 14 publications

References 53 publications

Differential LysoTracker Uptake Defines Two Populations of Distal Epithelial Cells in Idiopathic Pulmonary Fibrosis

Differential LysoTracker Uptake Defines Two Populations of Distal Epithelial Cells in Idiopathic Pulmonary Fibrosis

Temporal expression pattern of genes during the period of sex differentiation in human embryonic gonads

ETV5 regulates ductal morphogenesis with Sox9 and is critical for regeneration from pancreatitis

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