title: Perturbed hematopoiesis in mice lacking ATMIN.
abstract: The ataxia telangiectasia mutated (ATM)-interacting protein ATMIN mediates noncanonical ATM signaling in response to oxidative and replicative stress conditions. Like ATM, ATMIN can function as a tumor suppressor in the hematopoietic system: deletion of Atmin under the control of CD19-Cre results in B-cell lymphomas in aging mice. ATM signaling is essential for lymphopoiesis and hematopoietic stem cell (HSC) function; however, little is known about the role of ATMIN in hematopoiesis. We thus sought to investigate whether the absence of ATMIN would affect primitive hematopoietic cells in an ATM-dependent or -independent manner. Apart from its role in B-cell development, we show that ATMIN has an ATM-independent function in the common myeloid progenitors (CMPs) by deletion of Atmin in the entire hematopoietic system using Vav-Cre. Despite the lack of lymphoma formation, ATMIN-deficient mice developed chronic leukopenia as a result of high levels of apoptosis in B cells and CMPs and induced a compensatory mechanism in which HSCs displayed enhanced cycling. Consequently, ATMIN-deficient HSCs showed impaired regeneration ability with the induction of the DNA oxidative stress response, especially when aged. ATMIN, therefore, has multiple roles in different cell types, and its absence results in perturbed hematopoiesis, especially during stress conditions and aging.
authors: Haematopoietic Stem Cell Laboratory, The Francis Crick Institute, Lincoln's Inn Fields Laboratory, London, United Kingdom.|Haematopoietic Signalling Group, European Cancer Stem Cell Research Institute, School of Biosciences, Cardiff University, Cardiff, United Kingdom.
authors: Fernando
authors: F
authors: Anjos-Afonso
authors: Mammalian Genetics Laboratory, The Francis Crick Institute, Lincoln's Inn Fields Laboratory, London, United Kingdom.|Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
authors: Joanna I
authors: JI
authors: Loizou
authors: Haematopoietic Stem Cell Laboratory, The Francis Crick Institute, Lincoln's Inn Fields Laboratory, London, United Kingdom.
authors: Amy
authors: A
authors: Bradburn
authors: Mammalian Genetics Laboratory, The Francis Crick Institute, Lincoln's Inn Fields Laboratory, London, United Kingdom.|Translational Cancer Therapeutics Laboratory, UCL Cancer Institute, University College London, London, United Kingdom.
authors: Nnennaya
authors: N
authors: Kanu
authors: Flow Cytometry Laboratory, The Francis Crick Institute, Lincoln's Inn Fields Laboratory, London, United Kingdom; and.
authors: Sukhveer
authors: S
authors: Purewal
authors: Mammalian Genetics Laboratory, The Francis Crick Institute, Lincoln's Inn Fields Laboratory, London, United Kingdom.
authors: Clive
authors: C
authors: Da Costa
authors: Haematopoietic Stem Cell Laboratory, The Francis Crick Institute, Lincoln's Inn Fields Laboratory, London, United Kingdom.
authors: Dominique
authors: D
authors: Bonnet
authors: Mammalian Genetics Laboratory, The Francis Crick Institute, Lincoln's Inn Fields Laboratory, London, United Kingdom.|Diabetes & Nutritional Sciences Division, Faculty of Life Sciences & Medicine, King's College London, London, United Kingdom.
authors: Axel
authors: A
authors: Behrens
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D002908:Chronic Disease; D017353:Gene Deletion; D006410:Hematopoiesis / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology; D007970:Leukopenia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C554480:ATMIN protein, mouse; D014157:Transcription Factors; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse