MiR-9-1 controls osteoblastic regulation of lymphopoiesis

Yongguang Zhang, Danfeng Lin, Yongwei Zheng, Yuhong Chen, Mei Yu, Dongya Cui, Miaohui Huang, Xinlin Su, Yong Sun, Yabing Chen, Zhijian Qian, Karen Sue Carlson, Renren Wen, Demin Wang

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

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. [Figure not available: see fulltext.]

Original languageEnglish (US)
Pages (from-to)2261-2275
Number of pages15
JournalLeukemia
Volume37
Issue number11
DOIs
StatePublished - Nov 2023
Externally publishedYes

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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