Perturbed hematopoiesis in mice lacking ATMIN.

Area of Science:

• Molecular Biology
• Hematology
• Cell Biology

Background:

• The ataxia telangiectasia mutated (ATM)-interacting protein ATMIN mediates noncanonical ATM signaling in response to oxidative and replicative stress.
• ATMIN, similar to ATM, acts as a tumor suppressor in the hematopoietic system, with its deletion leading to B-cell lymphomas in mice.
• While ATM signaling is vital for lymphopoiesis and hematopoietic stem cell (HSC) function, ATMIN's specific role in hematopoiesis remains largely unexplored.

Purpose of the Study:

• To investigate the role of ATMIN in primitive hematopoietic cells.
• To determine if ATMIN's function in hematopoiesis is ATM-dependent or independent.

Main Methods:

• Deletion of Atmin in hematopoietic cells using CD19-Cre and Vav-Cre mouse models.
• Analysis of hematopoietic cell populations, apoptosis levels, and HSC cycling and regeneration.
• Assessment of DNA oxidative stress response in aged ATMIN-deficient HSCs.

Main Results:

• ATMIN exhibits an ATM-independent function in common myeloid progenitors (CMPs).
• ATMIN-deficient mice develop chronic leukopenia due to increased apoptosis in B cells and CMPs.
• ATMIN deficiency leads to enhanced HSC cycling, impaired HSC regeneration, and induced DNA oxidative stress response, especially in aged mice.

Conclusions:

• ATMIN plays multifaceted roles in different hematopoietic cell types.
• Absence of ATMIN perturbs hematopoiesis, particularly affecting B cells and CMPs, and compromises HSC function under stress and aging conditions.