AUTHOR=Gao Juan , Hou Shuaibing , Yuan Shengnan , Wang Yuxia , Gao Yanan , Sun Xiaolu , Wang Weili , Chu Yajing , Zhou Yuan , Feng Xiaoming , Luo Hongbo R. , Cheng Tao , Shi Jun , Yuan Weiping , Wang Xiaomin 

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

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.650599

DOI=10.3389/fcell.2021.650599

ISSN=2296-634X

ABSTRACT=<p>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 <italic>Vav1-Cre;Rheb1<sup><italic>f</italic><italic>l/fl</italic></sup></italic> mice. Here, using <italic>in vivo</italic> and <italic>in vitro</italic> models, we found that <italic>Rheb1</italic>-deficient neutrophils remodeled the bone marrow environment and induced expansion of HSCs <italic>in vivo</italic>. 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.</p>