Runx1 and Runx2 inhibit fibrotic conversion of cellular niches for hematopoietic stem cells

Journal	Nat. Commun. 13(1):2654 (2022)
Title	Runx1 and Runx2 inhibit fibrotic conversion of cellular niches for hematopoietic stem cells
Laboratory	Laboratory of Stem Cell Biology and Developmental Immunology〈Prof. NAGASAWA Takashi〉

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.

Authors	Yoshiki Omatsu (1, 2, 3), Shota Aiba (1, 2, 3), Tomonori Maeta (1, 2, 3), Kei Higaki (1, 2, 3), Kazunari Aoki (4), Hitomi Watanabe (5), Gen Kondoh (5), Riko Nishimura (6), Shu Takeda (7), Ung-Il Chung (8), Takashi Nagasawa (1, 2, 3) Laboratory of Stem Cell Biology and Developmental Immunology, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka, 565-0871, Japan. Laboratory of Stem Cell Biology and Developmental Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan. Laboratory of Stem Cell Biology and Developmental Immunology, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka, 565-0871, Japan. Laboratory of Stem Cell Genetics, Institute for Frontier Life and Medical Sciences, Kyoto University, Sakyo-ku, Kyoto, 606-8507, Japan. Laboratory of Animal Experiments for Regeneration, Institute for Frontier Life and Medical Sciences, Kyoto University, Sakyo-ku, Kyoto, 606-8507, Japan. Department of Molecular and Cellular Biochemistry, Graduate School of Dentistry, Osaka University, Suita, Osaka, 565-0871, Japan. Endocrinology Division, Toranomon Hospital, Minato-ku, Tokyo, 105-8470, Japan. Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Bunkyo-ku, Tokyo, 113-8656, Japan.
PubMed	35551452

Authors

Yoshiki Omatsu (1, 2, 3), Shota Aiba (1, 2, 3), Tomonori Maeta (1, 2, 3), Kei Higaki (1, 2, 3), Kazunari Aoki (4), Hitomi Watanabe (5), Gen Kondoh (5), Riko Nishimura (6), Shu Takeda (7), Ung-Il Chung (8), Takashi Nagasawa (1, 2, 3)

Laboratory of Stem Cell Biology and Developmental Immunology, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka, 565-0871, Japan.
Laboratory of Stem Cell Biology and Developmental Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan.
Laboratory of Stem Cell Biology and Developmental Immunology, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka, 565-0871, Japan.
Laboratory of Stem Cell Genetics, Institute for Frontier Life and Medical Sciences, Kyoto University, Sakyo-ku, Kyoto, 606-8507, Japan.
Laboratory of Animal Experiments for Regeneration, Institute for Frontier Life and Medical Sciences, Kyoto University, Sakyo-ku, Kyoto, 606-8507, Japan.
Department of Molecular and Cellular Biochemistry, Graduate School of Dentistry, Osaka University, Suita, Osaka, 565-0871, Japan.
Endocrinology Division, Toranomon Hospital, Minato-ku, Tokyo, 105-8470, Japan.
Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Bunkyo-ku, Tokyo, 113-8656, Japan.

PubMed

35551452