Project description:The fate options of hematopoietic stem cells (HSCs) include self-renewal, differentiation, migration and apoptosis, but the interaction between intracellular Ca2+ and cytoplasmic chaperon protein in regulating fate options of long term-HSCs (LT-HSC) is unknown. We created a S100A6 conditional knockout mouse model in the hematopoietic system and our studies showed that in S100A6KO, the number of LT-HSCs was significantly reduced and HSCs engrafted poorly. After 5FU challenge, the frequency of S100A6KO HSCs remained significantly low. Our data showed that S100A6 failed to self-renew through Akt pathway in an intracellular calcium (Cai2+)-dependent manner. Expression profiling of S100A6KO obtained from gene signatures revealed that cytosolic calcium level and proteins translocation to mitochondria were decreased. Mitochondrial oxidative phosphorylation was impaired in S100A6KO. Proteomic data indicated Hsp90 protein and chaperonin family were reduced. Our findings demonstrated that S100A6 regulates fate options of HSCs self-renewal through integrating Akt signaling, specifically governing mitochondria metabolic function and protein quality.
Project description:Purpose: Gene expression profiling of long term hematopoietic stem cells (LT-HSCs) transduced with Kat6b shRNA and Non-Targeting Control (NTC)
Project description:Analysis of highly purified long-term hematopoietic stem cells (LT-HSCs) 2 hours after irradiation at 0Gy, 0.02Gy and 2.5Gy. Results provide insight into the molecular mechanisms underlying LT-HSCs immediate response to low doses of γ-irradiation compared to high doses. Three samples were analyzed and correlated with the control group (0Gy).
Project description:Analysis of highly purified long-term hematopoietic stem cells (LT-HSCs) 2 hours after irradiation at 0Gy, 0.02Gy and 2.5Gy. Results provide insight into the molecular mechanisms underlying LT-HSCs immediate response to low doses of γ-irradiation compared to high doses.
Project description:Ppm1d T/+ mice exhibit altered BM composition. The aim is to determine the molecular mechanisms possibly responsible for this alterations in sorted long-term hematopoietic stem cells isolated from bone marrow. Long-term HSCs (LT-HSCs sorted from 12-week-old WT and Ppm1DT/+ mice. The Ppm1dT/+ HSC transcriptome shows enrichment of MYC, mTOR compared to WT.
Project description:Analysis of highly purified long-term hematopoietic stem cells (LT-HSCs) irradiated at 0Gy, 0.02Gy, 0.1Gy and 0.5Gy six months after transplantation. Results provide insight into the molecular mechanisms underlying multiple aspects of LT-HSCs premature ageing after low doses of γ-irradiation (0.02Gy). Four samples were analyzed and correlated with the control group (0Gy).
Project description:Analysis of highly purified long-term hematopoietic stem cells (LT-HSCs) irradiated at 0Gy, 0.02Gy, 0.1Gy and 0.5Gy six months after transplantation. Results provide insight into the molecular mechanisms underlying multiple aspects of LT-HSCs premature ageing after low doses of γ-irradiation (0.02Gy).
Project description:Self-renewal is a defining characteristic of stem cells, however the molecular pathways underlying its regulation are poorly understood. Here we demonstrate that conditional inactivation of the Pbx1 proto-oncogene in the hematopoietic compartment results in a progressive loss of long-term hematopoietic stem cells (LT-HSCs) that is associated with concomitant reduction in their quiescence, leading to a defect in the maintenance of self-renewal as assessed by serial transplantation. Transcriptional profiling revealed that multiple stem cell maintenance factors are perturbed in Pbx1-deficient LT-HSCs, which prematurely express a large subset of genes, including cell cycle regulators, normally expressed in non-self-renewing multipotent progenitors. A significant proportion of Pbx1-dependent genes are associated with the Tgf-b pathway, which serves a major role in maintaining HSC quiescence. Pbx1-deficient LT-HSCs are unable to up-regulate the cyclin dependent kinase inhibitor p57 in response to Tgf-b, providing a mechanism through which Pbx1 maintenance of stem cell self-renewal is achieved. Experiment Overall Design: Highly efficient Pbx1 deletion was induced with poly(I:C) in 3 young MxCre+.Pbx1f/f mutant or 2 MxCre-.Pbx1f/f control mice. LT-HSC (Lin-cKit+Sca1+CD34-CD135-) cells were prospectively sorted from bone marrow of individual mice harvested 4 weeks after the last injection of poly(I:C).
Project description:Here we addressed the mRNA transcriptome of Long-Term Hematopoietic Stem Cells (LT-HSC) and Multipotent Progenitor (MPP) -3 and -4 purified from WT and Helios KO mice. By analyzing the differentially expressed genes among WT and KO condition we found that Helios deletion affects transcription mostly in the LT-HSC compartment and favor a megakaryocyte mRNA lineage priming at the expense of the lymphoid one.
