Mouse model of X–linked chronic granulomatous disease, an inherited defect in phagocyte superoxide production
Gene targeting was used to generate mice with a null allele of the gene involved in X–linked CGD, which encodes the 91 kD subunit of the oxidase cytochrome b, and affected hemizygous male mice lacked phagocyte superoxide production and had an altered inflammatory response in thioglycollate peritonitis.
Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts
Results indicate that haematopoietic stem cells do not readily acquire a cardiac phenotype, and raise a cautionary note for clinical studies of infarct repair.
Rac1 Activation Controls Nuclear Localization of β-catenin during Canonical Wnt Signaling
Hematopoietic Cell Regulation by Rac1 and Rac2 Guanosine Triphosphatases
The deletion of both Rac1 and Rac2 murine alleles leads to a massive egress of hematopoietic stem/progenitor cells into the blood from the marrow, whereas Rac1–/– but not Rac2-/– HSC/Ps fail to engraft in the bone marrow of irradiated recipient mice.
Exit from dormancy provokes DNA-damage-induced attrition in haematopoietic stem cells
This work shows in mice that DNA damage is a direct consequence of inducing HSCs to exit their homeostatic quiescent state in response to conditions that model physiological stress, such as infection or chronic blood loss, and provides a mechanistic explanation for the universal accumulation of DNA damage in H SCs during ageing and the accelerated failure of the haematopoietic system in Fanconi anaemia patients.
Modulating the stem cell niche for tissue regeneration
It is envisaged that successful treatments in regenerative medicine will involve different combinations of factors to target stem cells and niche cells, applied at different times to effect recovery according to the dynamics of stem cell–niche interactions.
Highly efficient therapeutic gene editing of human hematopoietic stem cells
Optimized conditions for ribonucleoprotein delivery of Cas9–sgRNA complexes enables precise and efficient gene editing to restore fetal hemoglobin expression in sickle cell disease patient-derived HSCs.
Critical Roles for Rac1 and Rac2 GTPases in B Cell Development and Signaling
In the absence of both Rac1 and the highly related Rac2, B cell development was almost completely blocked and both GTPases were required to transduce BCR signals leading to proliferation, survival and up-regulation of BAFF-R, a receptor for BAFF, a key survival molecule required for Bcell development and maintenance.
Impaired FANCD2 monoubiquitination and hypersensitivity to camptothecin uniquely characterize Fanconi anemia complementation group M.
FANCM functions in an FA core complex-dependent and -independent manner, and a C-terminal deletion mutant rescued the cross-linker sensitivity of FancM(-/-) cells, whereas a FANCM ATPase mutant did not.