Runx1 and Runx2 Inhibit Fibrotic Conversion of Cellular Niches for Hematopoietic Stem Cells

Overview

Journal Nat Commun

Specialty Biology

Date 2022 May 13

PMID 35551452

Authors

Yoshiki Omatsu

Shota Aiba

Tomonori Maeta

Kei Higaki

Kazunari Aoki

Hitomi Watanabe

Gen Kondoh

Riko Nishimura

Shu Takeda

Ung-Il Chung

Takashi Nagasawa

Affiliations

Soon will be listed here.

Abstract

In bone marrow, special microenvironments, known as niches, are essential for the maintenance of hematopoietic stem cells (HSCs). A population of mesenchymal stem cells, termed CXC chemokine ligand 12 (CXCL12)-abundant reticular (CAR) cells or leptin receptor-expressing cells are the major cellular component of HSC niches. The molecular regulation of HSC niche properties is not fully understood. The role of Runx transcription factors, Runx1 and Runx2 in HSC cellular niches remains unclear. Here we show that Runx1 is predominantly expressed in CAR cells and that mice lacking both Runx1 and Runx2 in CAR cells display an increase in fibrosis and bone formation with markedly reduced hematopoietic stem and progenitor cells in bone marrow. In vitro, Runx1 is induced by the transcription factor Foxc1 and decreases fibrotic gene expression in CAR cells. Thus, HSC cellular niches require Runx1 or Runx2 to prevent their fibrotic conversion and maintain HSCs and hematopoiesis in adults.

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