Omatsu Yoshiki, Nagasawa Takashi
aDepartment of Immunobiology and Hematology, Institute for Frontier Medical Sciences, Kyoto University bJapan Science and Technology Agency (JST), Core Research for Evolutional Science and Technology (CREST), Kyoto, Japan.
Curr Opin Hematol. 2015 Jul;22(4):330-6. doi: 10.1097/MOH.0000000000000153.
It has been assumed that the special microenvironments known as niches in the marrow play an essential role in maintaining hematopoietic stem and progenitor cells (HSPCs), and the identity of the HSPC niche has been a subject of long-standing debate. Recent studies identified cells, which create microenvironments meeting the criteria for HSPC niches and the critical transcriptional regulators of their development and maintenance.
Osterix as well as Ebf2 and Bmi1 are critical but not specific transcriptional regulators of HSPC niche development. The transcription factor Foxc1 is expressed preferentially in a population of adipo-osteogenic progenitors, termed CXCL12-abundant reticular (CAR) cells, which create HSPC niches and are largely equivalent to stem cell factor and Lepr-expressing cells, in developing and adult bone marrow. Foxc1 is essential for CAR cell development and maintenance of bone marrow niches for HSPCs upregulating CXCL12 and SCF expression and inhibition of adipogenic processes in CAR cell progenitors.
Foxc1 is the first critical and specific transcriptional regulator that is required for development and maintenance of cells creating HSPC niches, including a specialized population of adipo-osteogenic progenitors in bone marrow.
人们一直认为，骨髓中被称为龛位的特殊微环境在维持造血干细胞和祖细胞（HSPCs）方面起着至关重要的作用，而HSPC龛位的身份一直是长期争论的主题。最近的研究确定了一些细胞，它们创造出符合HSPC龛位标准的微环境以及其发育和维持的关键转录调节因子。
osterix以及Ebf2和Bmi1是HSPC龛位发育的关键但非特异性转录调节因子。转录因子Foxc1优先在一群脂肪成骨祖细胞中表达，这群细胞被称为富含CXCL12的网状（CAR）细胞，它们在发育中和成年骨髓中创造HSPC龛位，并且在很大程度上等同于表达干细胞因子和Lepr的细胞。Foxc1对于CAR细胞的发育以及维持HSPCs的骨髓龛位至关重要，它上调CXCL12和SCF的表达，并抑制CAR细胞祖细胞中的脂肪生成过程。
Foxc1是第一个对于创造HSPC龛位的细胞（包括骨髓中一群特殊的脂肪成骨祖细胞）的发育和维持所必需的关键且特异性的转录调节因子。
