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GSE18393
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Ihh expression is required for intestinal stem cell niche development.
Publication Title
Indian hedgehog regulates intestinal stem cell fate through epithelial-mesenchymal interactions during development.
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Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
NextSeq 500
Description
Aging is a major risk factor for both genetic and sporadic neurodegenerative disorders. However, it is unclear how aging interacts with genetic predispositions to promote neurodegeneration. Here we investigate how partial loss-of-function of TBK1, a major genetic cause for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) comorbidity, leads to age-dependent neurodegeneration. We show that TBK1 is an endogenous inhibitor of RIPK1 and the embryonic lethality of Tbk1-/- mice is dependent on RIPK1 kinase activity. In aging human brains, another endogenous RIPK1 inhibitor, TAK1, exhibits a marked decrease in expression. We show that in Tbk1+/- mice, the reduced myeloid TAK1 expression promotes all the key hallmarks of ALS/FTD, including neuroinflammation, TDP-43 aggregation, axonal degeneration, neuronal loss and behavior deficits, which are blocked upon inhibition of RIPK1. Thus, aging facilitates RIPK1 activation by reducing TAK1 expression, which cooperates with genetic risk factors to promote the onset of ALS/FTD. Overall design: mRNA profiles of primary microglia derived from 2-day old wild type (WT), Tbk1+/-, Tbk1+/-;Ripk1D138N/D138N, Tak1?M/+, Tbk1+/-;Tak1?M/+ and Tbk1+/-;Tak1?M/+;RIpk1D138N/+ mice were generated by bulk RNA sequencing, in triplicate.
Publication Title
TBK1 Suppresses RIPK1-Driven Apoptosis and Inflammation during Development and in Aging.
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