MiR-9-1 controls osteoblastic regulation of lymphopoiesis.
Yongguang ZhangDanfeng LinYongwei ZhengYuhong ChenMei YuDongya CuiMiaohui HuangXinlin SuYong SunYabing ChenZhijian QianKaren-Sue CarlsonRenren WenDemin WangPublished in: Leukemia (2023)
The highly conserved MicroRNA-9 (miR-9) family consists of three members. We discovered that miR-9-1 deletion reduced mature miR-9 expression, causing 43% of the mice to display smaller size and postweaning lethality. MiR-9-1-deficient mice with growth defects experienced severe lymphopenia, but other blood cells were unaffected. The lymphopenia wasn't due to defects in hematopoietic progenitors, as mutant bone marrow (BM) cells underwent normal lymphopoiesis after transplantation into wild-type recipients. Additionally, miR-9-1-deficient mice exhibited impaired osteoblastic bone formation, as mutant mesenchymal stem cells (MSCs) failed to differentiate into osteoblastic cells (OBs). RNA sequencing revealed reduced expression of master transcription factors for osteoblastic differentiation, Runt-related transcription factor 2 (Runx2) and Osterix (Osx), and genes related to collagen formation, extracellular matrix organization, and cell adhesion, in miR-9-1-deficient MSCs. Follistatin (Fst), an antagonist of bone morphogenetic proteins (BMPs), was found to be a direct target of miR-9-1. Its deficiency led to the up-regulation of Fst, inhibiting BMP signaling in MSCs, and reducing IL-7 and IGF-1. Thus, miR-9-1 controls osteoblastic regulation of lymphopoiesis by targeting the Fst/BMP/Smad signaling axis.
Keyphrases
- cell proliferation
- long non coding rna
- mesenchymal stem cells
- transcription factor
- long noncoding rna
- poor prognosis
- bone marrow
- wild type
- induced apoptosis
- umbilical cord
- extracellular matrix
- cell cycle arrest
- type diabetes
- signaling pathway
- pi k akt
- cell death
- binding protein
- oxidative stress
- insulin resistance
- skeletal muscle
- genome wide
- stem cells
- soft tissue
- bioinformatics analysis
- growth hormone