TGFB in bone marrow dysfunction in diabetes
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE184612 | GEO | 2022/10/01
REPOSITORIES: GEO
Similar Datasets
Project description:TGFB in bone marrow dysfunction in diabetes
| PRJNA765364 | ENA
Project description:Bone marrow (BM) niche contributes to hematopoietic regeneration under stress like irradiation and leukemia. However, the mechanisms remain poorly defined. We here report that Lama4 deletion in mice results in reduction of mesenchymal progenitors (MPCs) and endothelial cells in BM. Following irradiation, Lama4-/- mice displayed impaired hematopoiesis recovery accompanied with dysregulation of BM niche factors like angiopoietin-1 and Tgfb1 in the MPCs. Post-transplantation of MLL-AF9 acute myeloid leukemia (AML) cells, we observed accelerated AML onset in Lama4-/- mice. Moreover, these Lama4-/- AML mice displayed faster relapse after therapeutic BM transplantation. Mechanistically, Lama4-/- niche promoted AML cell proliferation and chemoresistance to chemotherapy cytarabine by conferring AML greater antioxidant activity. Together, our study demonstrates that Lama4 is required to maintain hematopoietic niche integrity and to suppress AML progression and chemoresistance by restricting metabolic defense support to AML. Therefore, activating Lama4 signaling pathways may offer potential new therapeutic options for AML.
2022-02-16 | GSE167404 | GEO
Project description:Polycystic ovary syndrome (PCOS) is a female endocrine disorder characterized by hyperandrogenism, chronic anovulation, and polycystic ovaries. PCOS is often accompanied by symptoms such as insulin resistance, abdominal obesity, and chronic inflammation. Adipose tissue is a crucial endocrine organ involved in metabolic disorders. Metabolic issues and chronic inflammation in PCOS are linked to dysfunctional adipose tissue. Mesenchymal progenitor cells (MPCs) are the precursor cells of adipocytes and can regulate the immune system. In this study, we used induced pluripotent stem cells (iPSCs) from patients with PCOS to derive MPCs and compare the transcriptome profiles between PCOS and HC iPSC-derived MPCs. We also challenged iPSC-derived MPCs with testosterone to assess the impact of androgen on MPCs. We found that 1026 genes differed between PCOS and HC iPSC-derived MPCs. Gene set enrichment analysis showed adipogenesis and metabolic function were reduced, but the inflammatory response was raised in PCOS iPSC-derived MPCs. The critical signals for early adipogenesis, including TGFβ, BMP, WNT, and CEBPA, differed between PCOS and HC iPSC-derived MPCs. After adipogenic induction, mature adipocytes were lower in PCOS iPSC-derived MPCs than HC. Lipolysis, the process involved in fat metabolism, was lower in adipocytes derived from PCOS MPCs than in HC. The testosterone treatment results indicated that genes related to oxidative phosphorylation and fatty acid metabolism were upregulated in HC iPSC-derived MPCs but downregulated in PCOS iPSC-derived MPCs. Short-term androgen stimulation may benefit body functions in HC. The impact of testosterone varied among individuals with HC and PCOS, possibly because of a genetic tendency towards PCOS. This study explains important factors that help us understand PCOS.
2024-08-16 | GSE267287 | GEO
Project description:To explore the potential mechanism of chidamide in BM-MSC-mediated adipogenesis, we have employed mRNA microarray expression profiling platform to identify significant differential genes associated with adipogenic differentiation and chidamide management.
2022-04-13 | GSE199466 | GEO
Project description:Unlike ovarian cancer, normal ovarian epithelium response to TGFb1 induced growth inhibition. This study tried to idenify promoters that showed Smad4 binding after additionof TGFb1 in immortalized ovarian surface epithelial cells (IOSE) which is derived from normal ovarian epithelial cells Keywords: ChIP-chip
2007-01-13 | GSE6727 | GEO
Project description:TGFβ activates a signal transduction cascade that results in the microRNAs and genes transcription. The objective of this study is to identify miRNAs which are regulated through TGFB signaling pathway Cultured NHLF cells at 30-50% confluence were treated with 5 ng/mL TGFB1 or DMSO.
2013-01-04 | E-GEOD-27156 | biostudies-arrayexpress
Project description:Microglia diversity emerges from interactions between intrinsic genetic programs and environment-derived signals, but how these processes unfold and interact in the developing brain remains unclear. Here, we show that radial glia progenitor-expressed integrin beta 8 activates microglia-expressed TGFB1, permitting microglial development. Domain-restricted deletion of Itgb8 in these progenitors establishes complementary domains of developmentally arrested “dysmature” microglia and homeostatic microglia that persist into adulthood. In the absence of autocrine TGFB1 signaling, we find that microglia adopt a similar reactive microglial phenotype, leading to astrogliosis and neuromotor symptoms almost identical to Itgb8 mutant mice. By comparing mice with genetic deletions in critical components downstream of Itgb8, we show that non-canonical (Smad-independent) signaling partially suppresses the dysmature microglia phenotype, associated neuromotor dysfunction and expression of disease-associated genes, providing compelling evidence for the adoption of microglial develomental signaling pathways in the context of injury or disease.
2024-12-19 | GSE236615 | GEO
Project description:Mammals evolved in the face of fluctuating food availability. How the immune system adapts to transient nutritional stress remains poorly understood. Here, we show that memory T cells collapsed in secondary lymphoid organs in the context of dietary restriction (DR) but dramatically accumulated within the bone marrow (BM), where they adopted a state associated with energy conservation. This response was coordinated by glucocorticoids and associated with a profound remodeling of the BM compartment, which included an increase in T cell homing factors, erythropoiesis, and adipogenesis. Adipocytes and CXCR4-CXCL12 and S1P-S1P1R interactions contributed to enhanced T cell accumulation in BM during DR. Memory T cell homing to BM during DR was associated with enhanced protection against infections and tumors. Together, this work uncovers a fundamental host strategy to sustain and optimize immunological memory during nutritional challenges that involved a temporal and spatial reorganization of the memory pool within ‘‘safe haven’’ compartments.
2019-08-22 | GSE124063 | GEO
Project description:Gene expression profiling by cDNA microarray of bone marrow stromal cells from three healthy donors treated as follows: vehicle control; or stimulated with 10 nM substance P. Hematopoiesis is tightly regulated by the bone marrow (BM) niche. The niche is robust, allowing for the return of hematopoietic homeostasis after insults such as infection. Hematopoiesis is partly regulated by soluble factors such as neuropeptides, substance P (SP) and neurokinin A (NK-A), which mediate hematopoietic stimulation and inhibition, respectively. The hematopoietic effects of SP and NK-A are mostly mediated via BM stroma. Array analyses with 2400 genes indicated distinct changes in SP-stimulated BM stroma.
2019-05-18 | GSE131410 | GEO
Project description:Aims/hypothesisPrevious studies have shown that diabetes mellitus destabilises the integrity of the microvasculature in different organs by damaging the interaction between pericytes and endothelial cells. In bone marrow, pericytes exert trophic functions on endothelial cells and haematopoietic cells through paracrine mechanisms. However, whether bone marrow pericytes are a target of diabetes-induced damage remains unknown. Here, we investigated whether type 2 diabetes can affect the abundance and function of bone marrow pericytes.MethodsWe conducted an observational clinical study comparing the abundance and molecular/functional characteristics of CD146+ pericytes isolated from the bone marrow of 25 individuals without diabetes and 14 individuals with uncomplicated type 2 diabetes, referring to our Musculoskeletal Research Unit for hip reconstructive surgery.ResultsImmunohistochemistry revealed that diabetes causes capillary rarefaction and compression of arteriole size in bone marrow, without changing CD146+ pericyte counts. These data were confirmed by flow cytometry on freshly isolated bone marrow cells. We then performed an extensive functional and molecular characterisation of immunosorted CD146+ pericytes. Type 2 diabetes caused a reduction in pericyte proliferation, viability, migration and capacity to support in vitro angiogenesis, while inducing apoptosis. AKT is a key regulator of the above functions and its phosphorylation state is reportedly reduced in the bone marrow endothelium of individuals with diabetes. Surprisingly, we could not find a difference in AKT phosphorylation (at either Ser473 or Thr308) in bone marrow pericytes from individuals with and without diabetes. Nonetheless, the angiocrine signalling reportedly associated with AKT was found to be significantly downregulated, with lower levels of fibroblast growth factor-2 (FGF2) and C-X-C motif chemokine ligand 12 (CXCL12), and activation of the angiogenesis inhibitor angiopoietin 2 (ANGPT2). Transfection with the adenoviral vector carrying the coding sequence for constitutively active myristoylated AKT rescued functional defects and angiocrine signalling in bone marrow pericytes from diabetic individuals. Furthermore, an ANGPT2 blocking antibody restored the capacity of pericytes to promote endothelial networking.Conclusions/interpretationThis is the first demonstration of pericyte dysfunction in bone marrow of people with type 2 diabetes. An altered angiocrine signalling from pericytes may participate in bone marrow microvascular remodelling in individuals with diabetes.
| S-EPMC6560025 | biostudies-literature