한빛사논문
- 조회437
Jinguk Jeong1,2, Inkyung Jung3, Ji-Hoon Kim4, Shin Jeon1,5,7, Do Young Hyeon1, Hyungyu Min1,2, Byeonggeun Kang1,2, Jinwoo Nah1,2, Daehee Hwang1, Soo-Jong Um6, Myunggon Ko3,* and Rho Hyun Seong1,2,*
1School of Biological Sciences, Seoul National University, Seoul 08826, Korea. 2Institute of Molecular Biology and Genetics, Seoul National University, Seoul 08826, Korea. 3Department of Biological Sciences, Ulsan National Institute of Science and Technology, Ulsan 44919, Korea. 4Molecular Recognition Research Center, Korea Institute of Science and Technology, Seoul 02792, Korea. 5Department of Biological Sciences, University at Buffalo, Buffalo, NY 14260, USA. 6Department of Integrative Bioscience and Biotechnology, Sejong University, Seoul 05006, Korea. 7Present address: Department of Systems Pharmacology and Translational Therapeutics, Institute for Immunology, University of Pennsylvania, Philadelphia, PA 19104, USA.
*Corresponding author.
Abstract
Hematopoiesis occurs within a unique bone marrow (BM) microenvironment, which consists of various niche cells, cytokines, growth factors, and extracellular matrix components. These multiple components directly or indirectly regulate the maintenance and differentiation of hematopoietic stem cells (HSCs). Here we report that BAP1 in BM mesenchymal stromal cells (MSCs) is critical for the maintenance of HSCs and B lymphopoiesis. Mice lacking BAP1 in MSCs show aberrant differentiation of hematopoietic stem and progenitor cells, impaired B lymphoid differentiation, and expansion of myeloid lineages. Mechanistically, BAP1 loss in distinct endosteal MSCs, expressing PRX1 but not LEPR, leads to aberrant expression of genes affiliated with BM niche functions. BAP1 deficiency leads to a reduced expression of pro-hematopoietic factors such as Scf caused by increased H2AK119-ub1 and H3K27-me3 levels on the promoter region of these genes. On the other hand, the expression of myelopoiesis stimulating factors including Csf3 was increased by enriched H3K4-me3 and H3K27-ac levels on their promoter, causing myeloid skewing. Notably, loss of BAP1 substantially blocks B lymphopoiesis and skews the differentiation of hematopoietic precursors toward myeloid lineages in vitro, which is reversed by G-CSF neutralization. Thus, our study uncovers a key role for BAP1 expressed in endosteal MSCs in controlling normal hematopoiesis in mice by modulating expression of various niche factors governing lymphopoiesis and myelopoiesis via histone modifications.
논문정보
- Research article
- 2022년 04월 (BRIC 등록일 2022-05-10)
- 국내(교신)+국외 연구진
- 생명과학 > 면역학
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