Project description:5C-seq from Rad21lox/lox;NexCre/+ and Rad21+/+;NexCre/+ dissociated cortical neurons at Day In Vitro (DIV10) without stimulation or after treatment with TTX/D-AP5 and 1h of KCl depolarization. And, 5C of and doxycycline treated Rad21-TEV primary neurons transduced with NLS-TEV
Project description:We recently identified recurrent mutations of cohesin complex in myeloid neoplasms through whole-exome sequencing analysis. RAD21 is one of the main components of the cohesin complex. In this study, to investigate the biological impact of wild-type RAD21 on Kasumi1 cells harboring RAD21 mutation, Kasumi1 cells were retrovirally transduced with either mock or wild-type RAD21, and expression array was performed. Expression analysis was performed for mock- or wild-type RAD21-transduced Kasumi-1 cells in triplicate. The experiment was performed twice independently.
Project description:We recently identified recurrent mutations of cohesin complex in myeloid neoplasms through whole-exome sequencing analysis. RAD21 is one of the main components of the cohesin complex. In this study, to investigate the biological impact of wild-type RAD21 on Kasumi1 cells harboring RAD21 mutation, Kasumi1 cells were retrovirally transduced with either mock or wild-type RAD21, and expression array was performed.
Project description:MTD project_description Inflammation and decreased stem cell function characterize organism aging, yet the relationship between these factors remains incompletely understood. This study shows that aged hematopoietic stem and progenitor cells exhibit increased ground-stage NF-κB activity, which enhances their responsiveness to undergo differentiation and loss of self-renewal in response to inflammation. The study identifies Rad21/cohesin as a critical mediator of NF-κB signals, by increasing chromatin accessibility of inter-/intra-genic and enhancer regions. Rad21/NF-κB are required for normal differentiation, but limit self-renewal of hematopoietic stem cells (HSCs) during aging and inflammation in an NF-κB dependent manner. HSCs from aged mice fail to downregulate Rad21/cohesin and inflammation/differentiation inducing signals in the resolution phase after acute inflammation. and The inhibition of cohesin/NF-κB is sufficient to revert the hypersensitivity of aged HSPCs to inflammation-induced differentiation. During aging, myeloid-biased HSCs with disrupted and naturally occurring reduced expression of Rad21/cohesin are increasingly selected over lymphoid-biased HSCs. Together, Rad21/cohesin mediated NF-κB signaling limits HSPC function during aging and selects for cohesin deficient HSCs with myeloid skewed differentiation.
