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MiR-9-1 controls osteoblastic regulation of lymphopoiesis. Leukemia 2023 Nov;37(11):2261-2275

Date

09/06/2023

Pubmed ID

37670087

Pubmed Central ID

PMC10844005

DOI

10.1038/s41375-023-02014-8

Scopus ID

2-s2.0-85169811460 (requires institutional sign-in at Scopus site)   3 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.

Author List

Zhang Y, Lin D, Zheng Y, Chen Y, Yu M, Cui D, Huang M, Su X, Sun Y, Chen Y, Qian Z, Carlson KS, Wen R, Wang D

Authors

Karen-Sue B. Carlson MD, PhD Associate Professor in the Medicine department at Medical College of Wisconsin
Demin Wang PhD Professor in the Microbiology and Immunology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Bone Morphogenetic Proteins
Cell Differentiation
Lymphopenia
Lymphopoiesis
Mice
MicroRNAs
Osteoblasts
Osteogenesis