2. Academic Validation
  3. Rheb1-Deficient Neutrophils Promote Hematopoietic Stem/Progenitor Cell Proliferation via Mesenchymal Stem Cells

Rheb1-Deficient Neutrophils Promote Hematopoietic Stem/Progenitor Cell Proliferation via Mesenchymal Stem Cells

  • Front Cell Dev Biol. 2021 May 27;9:650599. doi: 10.3389/fcell.2021.650599.
Juan Gao 1 2,  Shuaibing Hou 1,  Shengnan Yuan 1,  Yuxia Wang 1,  Yanan Gao 1 3,  Xiaolu Sun 1,  Weili Wang 1,  Yajing Chu 1,  Yuan Zhou 1,  Xiaoming Feng 1,  Hongbo R Luo 4,  Tao Cheng 1,  Jun Shi 1,  Weiping Yuan 1,  Xiaomin Wang 1 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
  • 2 Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin Eye Hospital, Clinical College of Ophthalmology, Tianjin Eye Institute, Tianjin Medical University, Nankai University Affiliated Eye Hospital, Tianjin, China.
  • 3 Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China.
  • 4 Department of Pathology, Dana-Farber/Harvard Cancer Center, Harvard Medical School, Boston, MA, United States.
  • 5 Department of Neuro-Oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
PMID: 34124040 DOI: 10.3389/fcell.2021.650599
Abstract

Myeloid cells have been identified as hematopoietic stem cell (HSC)-regulating cells. However, the mechanisms by which myeloid cells regulate the function of HSCs are not fully defined. Our previous study indicated that the HSCs are over-expanded in Vav1-Cre;Rheb1 f l/fl mice. Here, using in vivo and in vitro models, we found that Rheb1-deficient neutrophils remodeled the bone marrow environment and induced expansion of HSCs in vivo. Further studies showed that loss of Rheb1 impaired neutrophils' ability to secrete IL-6, led mesenchymal stem cells (MSCs) to produce more SCF, and promote HSC proliferation. We further found that IL-6 suppressed SCF mRNA expression in human MSCs. Interesting, the high level of IL-6 was also related with poor survival of chronic myeloid leukemia (CML) patients, and higher expression of IL-6 in CML cells is associated with the lower expression of SCF in MSCs in patients. Our studies suggested that blocking IL-6 signaling pathway might stimulate MSCs to secrete more SCF, and to support hematopoietic stem/progenitor cells proliferation.

Keywords

IL-6; Rheb1-deficient neutrophils; hematopoietic stem/progenitor cell; mesenchymal stem cells; proliferation.

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