Runx family genes, niche, and stem cell quiescence

Runx3 deficiency results in myeloproliferative disorder in aged mice

“…RUNX1 is abrogated by multiple types of genetic alterations in human hematological malignancies [3][4][5] and is critical for the generation and maintenance of hematopoietic stem cells (HSCs). [6][7][8][9][10] Runx1 regulates the expression of stemnessand niche-related factors, such as Bmi1, Cxcr4, and integrin a 2 , deregulation of which in adult Runx1 knockout (KO) mice led to an expanded hematopoietic stem/progenitor cell (HSPC) compartment and subsequent stem cell exhaustion. [6][7][8][9][10][11][12] In addition, adult Runx1 KO mice show abnormal megakaryocytic differentiation and defective lymphoid development.…”

“…[6][7][8][9][10] Runx1 regulates the expression of stemnessand niche-related factors, such as Bmi1, Cxcr4, and integrin a 2 , deregulation of which in adult Runx1 knockout (KO) mice led to an expanded hematopoietic stem/progenitor cell (HSPC) compartment and subsequent stem cell exhaustion. [6][7][8][9][10][11][12] In addition, adult Runx1 KO mice show abnormal megakaryocytic differentiation and defective lymphoid development. [11][12][13][14] In contrast, the role of Runx3 in hematopoiesis remains elusive, despite the fact that Runx3 is expressed in various hematopoietic tissues in adult mice.…”

Genomic Promoter Occupancy of Runt-related Transcription Factor RUNX2 in Osteosarcoma Cells Identifies Genes Involved in Cell Adhesion and Motility

“…RUNX proteins control cell fate by regulating cell growth and differentiation of progenitor cells in different lineages (1)(2)(3). Deregulation of the function or expression of these factors is causally linked to distinct cancer phenotypes (4 -8).…”

“…Null mutations in Runt-related transcription factors (RUNX1/AML1, RUNX2/CBFA1, and RUNX3/ PEBP2␣C) cause major lineage-specific defects during mammalian development, although both loss-and gain-of-function mutations have been pathologically associated with cancer. For example, RUNX1 is frequently rearranged in acute myelogenous leukemia (1,2), and null mutations in mice abolish definitive hematopoiesis during fetal development (9 -11). Silencing of RUNX3 gene expression contributes to the etiology of carcinomas in multiple tissues (4,5), and loss-of-function mutations cause alterations in gastrointestinal and neuronal tissues during postnatal development (12)(13)(14).…”

An unsung runt 6e isoform for HSC expansion

“…4 Biological functional consequences of this RUNX1a-dependent inhibitory effect have since been extensively investigated in the field, particularly in the areas of HSCs and leukemia. 5,6 Through such endeavors over the past two decades, a significant body of knowledge has been accumulated, and we now know that the two FL forms, RUNX1b and RUNX1c, act as negative regulators for HSC pool size, and RUNX1a functions as a positive regulator (see figure). Fine-tuning of the balance between these positive and negative regulators transcribed from a single hematopoietic gene, RUNX1, is clearly shown to be one of the critical mechanisms in determining HSC population size.…”