Large-scale identification of genes implicated in kidney glomerulus development and function

Takemoto, Minoru; He, Liqun; Norlin, Jenny; Patrakka, Jaakko; Xiao, Zhijie; Petrova, Tatiana V.; Bondjers, Cecilia; Asp, Julia; Wallgard, Elisabet; Sun, Ying; Samuelsson, Tore; Mostad, Petter; Lundin, Samuel; Miura, Naoyuki; Sado, Yoshikazu; Alitalo, Kari; Quaggin, Susan E.; Tryggvason, Karl; Betsholtz, Christer

doi:10.1038/sj.emboj.7601014

Cited by 187 publications

(227 citation statements)

References 81 publications

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“…Previous studies showed that knockout of several transcription factors expressed in podocytes (Pod1, Foxc2, Limx1b, and Krm1/MafB) resulted in a decreased number of capillary loops and abnormal mesangium similar to what we observed in our study. [33][34][35][36] Therefore, S1P1 may be involved in the interactions among podocytes, ECs, and mesangium to regulate the development of the glomerular capillary loops. Whether S1P1 operates through the transcription factors mentioned earlier requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

Hemovascular Progenitors in the Kidney Require Sphingosine-1-Phosphate Receptor 1 for Vascular Development

Li²,

Göthert

et al. 2015

JASN

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The close relationship between endothelial and hematopoietic precursors during early development of the vascular system suggested the possibility of a common yet elusive precursor for both cell types. Whether similar or related progenitors for endothelial and hematopoietic cells are present during organogenesis is unclear. Using inducible transgenic mice that specifically label endothelial and hematopoietic precursors, we performed fate-tracing studies combined with colony-forming assays and crosstransplantation studies. We identified a progenitor, marked by the expression of helix-loop-helix transcription factor stem cell leukemia (SCL/Tal1). During organogenesis of the kidney, SCL/Tal1 + progenitors gave rise to endothelium and blood precursors with multipotential colony-forming capacity. Furthermore, appropriate morphogenesis of the kidney vasculature, including glomerular capillary development, arterial mural cell coating, and lymphatic vessel development, required sphingosine 1-phosphate (S1P) signaling via the G protein-coupled S1P receptor 1 in these progenitors. Overall, these results show that SCL/Tal1 + progenitors with hemogenic capacity originate and differentiate within the early embryonic kidney by hemovasculogenesis (the concomitant formation of blood and vessels) and underscore the importance of the S1P pathway in vascular development.

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Section: Discussionmentioning

confidence: 99%

Hemovascular Progenitors in the Kidney Require Sphingosine-1-Phosphate Receptor 1 for Vascular Development

Li²,

Göthert

et al. 2015

JASN

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“…GLCCI1 gene is highly expressed in lymph nodes, leukocytes, breast, testis, adrenal, lungs, kidneys and others [21]. Because of high glomerul expression [22] GLCCI1 rs37973 was also analysed on patients with nephrotic syndrome receiving oral steroids, however no pharmacogenetic association was found [23]. On lymphoblastoid B cells variants in GLCCI1 were shown to be associated with decreased expression of GLCCI1, both at baseline and in response to dexamethasone treatment [10].…”

Section: Discussionmentioning

confidence: 99%

GLCCI1 Polymorphism rs37973 and Response to Treatment of Asthma With Inhaled Corticosteroids

Rijavec¹,

Žavbi²,

Lopert³

et al. 2018

J Investig Allergol Clin Immunol

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Background. Asthma treatment response is highly variable and pharmacogenetic markers that predict treatment response would be one step closer to personalized treatment. GWAS studies have shown that polymorphisms GLCCI1 could be associated with asthma treatment response to inhaled corticosteroids (ICS).Materials and methods. We genotyped rs37973 of GLCCI1 in 208 adult asthma patients treated with ICS. Change in % predicted FEV1 was analysed after short-term (3 months) and after long-term (at least 3 years) treatment. Treatment success was defined as good when FEV1 decreased less than 30 ml/year.Results. After 3 months of treatment, change of % predicted FEV1 was higher in patients with GG genotype than in patients with AG+AA genotype, and this genotype dependent difference was only evident in non-smokers. Similar results were found after at least 3 years of treatment when all patients were analysed, in non-smokers and patients with atopy. Even though, no differences in treatment success (good vs. poor response) were observed when analysing the entire group of patients, genotype dependent treatment success was highly influenced by smoking and atopy. GG genotype was overrepresented in non-smokers and patients with atopy with good response.Conclusions. Rs37973 was associated with short-and long-term treatment response; however, there was a great influence of smoking and atopy on pharmacogenetic association. Furthermore, we found GG genotype to be associated with better treatment response, what is contrary to results found in GWAS.Keywords: pharmacogenetics, rs37973, GLCCI1, FEV1, smoking, atopy ResumenIntroducción: La respuesta al tratamiento del asma es muy variable y los marcadores farmacogenéticos que predicen esta respuesta nos sitúan más cerca del tratamiento personalizado. Los estudios de asociación de genoma completo (GWAS) han demostrado que los polimorfismos GLCCI1 podrían estar asociados con la respuesta al tratamiento con corticosteroides inhalados (ICS).Material y métodos. Se genotipó el polimorfismo de un solo nucleótico (SNP) rs37973 de GLCCI1 en 208 pacientes adultos con asma tratados con ICS. El cambio en el porcentual de lFEV1 predicho se analizó después de un tratamiento a corto plazo (3 meses) y después de un tratamiento a largo plazo (al menos 3 años). El éxito del tratamiento se definió como bueno cuando el FEV1 disminuyó menos de 30 ml / año.Resultados. Después de 3 meses de tratamiento, el cambio en el porcentual del FEV1 predicho fue mayor en pacientes con genotipo GG que en pacientes con genotipo AG + AA, y esta diferencia asociada al genotipo solo fue evidente en los no fumadores. Se encontraron resultados similares, en el análisis de la muestra completa de pacientes, después de al menos 3 años de tratamiento, tanto en no fumadores y como en pacientes atópicos. A pesar de que no se observaron diferencias en el éxito del tratamiento (buena frente a mala respuesta) al analizar todo el grupo de pacientes, el éxito del tratamiento dependiente del genotipo estuvo muy influenciado por el...

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“…This strategy can significantly increase the resolution of the screen. One approach has profiled small subsets of cells generated through dissection (Mitchell et al, 2006), cell sorting (Takemoto et al, 2006), or laser-capture microdissection (Potter et al, 2007). The resulting profile provides more specific information about the cell "state" of the profiled population.…”

Section: Profiling Cell Statementioning

confidence: 99%

Transcriptional profiling of Wnt4 mutant mouse kidneys identifies genes expressed during nephron formation

Valerius

McMahon

2008

Gene Expression Patterns

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The mature nephron forms from a simple epithelial vesicle into an elaborate structure with distinct regions of specialized physiological function. The molecular components driving the process of nephron development are not well understood. To identify genes that may be informative in this process we conducted a transcriptional profiling screen using Wnt4 mutant kidneys. In Wnt4 −/− homozygous mice, condensates and pretubular aggregates are induced, however, epithelial renal vesicles fail to form and subsequent tubulogenesis is blocked. A transcriptional profile comparison between wildtype and Wnt4−/− mutant kidneys at E14.5 was performed using Affymetrix oligonucleotide microarrays to identify nephron-expressed genes. This approach identified 236 genes with expression levels >1.8 fold higher in wildtype versus mutant kidneys, amongst these were a number of known nephron component markers confirming the validity of the screen. These results were further detailed by wholemount in situ hybridization (WISH) of E15.5 urogenital systems (UGS). We annotated the spatial expression pattern of these genes into eight categories of expression. Genes expressed in renal vesicle and their derivatives, structures absent in the mutant, accounted for the largest number of the observed expression patterns. A number of additional genes in areas not directly overlapping the Wnt4 expression domain were also identified including the cap mesenchyme, the collecting duct, and the cortical interstitium. This study provides a useful compendium of molecular markers for the study of nephrogenesis.

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Large-scale identification of genes implicated in kidney glomerulus development and function

Cited by 187 publications

References 81 publications

Hemovascular Progenitors in the Kidney Require Sphingosine-1-Phosphate Receptor 1 for Vascular Development

Hemovascular Progenitors in the Kidney Require Sphingosine-1-Phosphate Receptor 1 for Vascular Development

GLCCI1 Polymorphism rs37973 and Response to Treatment of Asthma With Inhaled Corticosteroids

Transcriptional profiling of Wnt4 mutant mouse kidneys identifies genes expressed during nephron formation

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