Title:
The microenvironmental niches for hematopoietic stem and progenitor cells in the bone marrow

 

Speaker:
Takashi Nagasawa
Laboratory of Stem Cell Biology and Developmental Immunology,
Graduate School of Frontier Biosciences and Graduate School of Medicine, Osaka University

 

Abstract:
All blood cells, including immune cells, are generated from hematopoietic stem cells (HSCs) in the bone marrow. HSCs are in contact with and maintained by restricted microenvironments, termed niches; however, the identity of cells creating HSC niches has been a subject of longstanding debate. We focused our analysis on the chemokine CXCL12, which is essential for homing and maintenance of HSCs and development of immune cells in the bone marrow, and identified a population of mesenchymal cells with long processes, expressing high amounts of CXCL12, termed CXCL12-abundant reticular (CAR) cells. We revealed that most HSCs adjoined the processes of CAR cells and that ablation of CAR cells in vivo severely impaired the adipogenic and osteogenic differentiation potential of bone marrow cells and production of stem cell factor (SCF) as well as CXCL12, and led to a marked reduction in the numbers of hematopoietic stem and progenitor cells (HSPCs), indicating that CAR cells are adipo-osteogenic progenitors, which create a HSPC niche. Recently, we found that the transcription factor Foxc1 was preferentially expressed in CAR cells in the bone marrow and was essential for development and maintenance of the HSPC niche, enhancing CXCL12 and SCF expression, and inhibiting adipogenic processes in CAR cells. The features of cells, which play a dominant role in creating HSC niches in the bone marrow will be discussed.

 

References:
(1) Sugiyama, T. et al., Immunity 25, 977 (2006).
(2) Omatsu, Y. et al., Immunity 33, 387 (2010).
(3) Omatsu, Y. et al., Nature 508, 536 (2014).