1. |
- Chen, Wei-Ting, et al.
(författare)
-
Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer's Disease
- 2020
-
Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 182:4, s. 976-
-
Tidskriftsartikel (refereegranskat)abstract
- Although complex inflammatory-like alterations are observed around the amyloid plaques of Alzheimer's disease (AD), little is known about the molecular changes and cellular interactions that characterize this response, We investigate here, in an AD mouse model, the transcriptional changes occurring in tissue domains in a 100-mu m diameter around amyloid plaques using spatial transcriptomics. We demonstrate early alterations in a gene co-expression network enriched for myelin and oligodendrocyte genes (OLIGs), whereas a multicellular gene co-expression network of plaque-induced genes (PIGs) involving the complement system, oxidative stress, lysosomes, and inflammation is prominent in the later phase of the disease. We confirm the majority of the observed alterations at the cellular level using in situ sequencing on mouse and human brain sections. Genome-wide spatial transcriptomics analysis provides an unprecedented approach to untangle the dysregulated cellular network in the vicinity of pathogenic hallmarks of AD and other brain diseases.
|
|
2. |
- Raja, Erna, et al.
(författare)
-
The protein kinase LKB1 negatively regulates bone morphogenetic protein receptor signaling
- 2016
-
Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:2, s. 1120-1143
-
Tidskriftsartikel (refereegranskat)abstract
- The protein kinase LKB1 regulates cell metabolism and growth and is implicated in intestinal and lung cancer. Bone morphogenetic protein (BMP) signaling regulates cell differentiation during development and tissue homeostasis. We demonstrate that LKB1 physically interacts with BMP type I receptors and requires Smad7 to promote downregulation of the receptor. Accordingly, LKB1 suppresses BMP-induced osteoblast differentiation and affects BMP signaling in Drosophila wing longitudinal vein morphogenesis. LKB1 protein expression and Smad1 phosphorylation analysis in a cohort of non-small cell lung cancer patients demonstrated a negative correlation predominantly in a subset enriched in adenocarcinomas. Lung cancer patient data analysis indicated strong correlation between LKB1 loss-of-function mutations and high BMP2 expression, and these two events further correlated with expression of a gene subset functionally linked to apoptosis and migration. This new mechanism of BMP receptor regulation by LKB1 has ramifications in physiological organogenesis and disease.
|
|