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VPS72 primes B-lymphoid gene expression and limits myeloid output during hematopoietic stem cell development 4135

Year: 2025
Type: conference-abstract
Abstract: Description VPS72 incorporates H2AZ to nucleosome that regulates gene activity by modifying chromatin architecture. Increased expression of VPS72 has been reported in hematopoietic stem cells (HSC). However, the mechanism by which VPS72 modulates the fate decision of HSCs in mammalian hematopoiesis remains unknown. The objective of this study is to characterize the role of VPS72 in HSC function, maintenance, and development. We generated hematopoietic-specific poly IC-inducible VPS72-knockout (VPS72iKO) mice using widely used Mx1-cre mice. Single-cell suspensions of bone marrow (BM) and spleen were processed. Flow cytometry, Bulk RNA-Seq and scATAC-seq were performed. The frequencies of long-term and short-term HSC, lympho-myeloid primed progenitor and megakaryocyte/erythroid progenitor were decreased, whereas common myeloid progenitor and granulocyte/monocyte progenitor were increased in VPS72iKO mice compared to wild type mice. Further, VPS72-deficient BM exhibited higher frequencies of myeloid cells with the loss of B cells. VPS72 loss promoted the expression of myeloid related genes including Cebpa, and cell proliferation related gene, E2F. Overall, VPS72 loss markedly caused alteration of hematopoietic differentiation compatible with increase myeloid output than lymphoid, suggesting that VPS72 is required for HSC maintenance or differentiation. Understanding the regulatory pathway of VPS72 provides valuable insight into the balance between normal and pathological hematopoiesis. Funding Sources NIH/NIAID Topic Categories Hematopoiesis and Immune System Development (HEM)
DOI: 10.1093/jimmun/vkaf283.1856
Language: English
Subfield: Hematology
Field: Medicine
Open Access status: bronze
OpenAlex ID: W4416448940
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