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HOXA9
Homeobox protein Hox-A9 is a protein that in humans is encoded by the HOXA9 gene.
In vertebrates, the genes encoding the class of transcription factors called homeobox genes are found in clusters named A, B, C, and D on four separate chromosomes. Expression of these proteins is spatially and temporally regulated during embryonic development. This gene is part of the A cluster on chromosome 7 and encodes a DNA-binding transcription factor which may regulate gene expression, morphogenesis, and differentiation. This gene is highly similar to the abdominal-B (Abd-B) gene of Drosophila fly. A specific translocation event which causes a fusion between this gene and the NUP98 gene has been associated with myeloid leukemogenesis.
As HOXA9 dysfunction has been implicated in acute myeloid leukemia, and expression of the gene has been shown to differ markedly between erythrocyte lineages of different stages of development, the gene is of particular interest from a hematopoietic perspective.
As HOXA9 is part of the homeobox family, involved in setting the body plans of animals, it is likely that HOXA9 would display increased expression in cells with higher differentiation potentials. Indeed in the hematopoietic lineage, it has been found that HOXA9 is preferentially expressed in hematopoietic stem cells (HSCs), and is down-regulated as the cell differentiates and matures further.
HOXA9 knockout mice have been shown to develop a reduction in the number of circulating common myeloid progenitor cells, which differentiate into erythroid progenitor cells. The same study indicated that HOXA9 deficiencies specifically affected the granulocyte lineage of the common myeloid progenitor, and it was in HOXA7 knockout mice where the erythroid lineage was affected; however, ErythronDB shows HOXA7 as being insignificantly expressed in all stages of each erythroid lineage. This is something that needs to be investigated further, and could shed light on the interactions between the genes in the HOXA family.
Another study found that HOXA9 knockout HSCs displayed a 5-fold impairment to proliferation rate in vitro, as well as delayed maturation to committed progenitors, specifically myeloid maturation, and that normal proliferation and differentiation rates could be reinstated by reintroducing a HOXA9 vector into the culture. In vivo, lethally irradiated mice with transplanted HOXA9 knockout HSCs displayed a 4-fold to 12-fold reduction in repopulating ability. Furthermore, they developed 60% less myeloid and erythroid colonies in the bone marrow when compared to the wild type. Furthermore, transgenic mice with overexpressed HOXA9 developed a 15-fold increase in the amount of committed progenitor cells in the bone marrow, indicating that overexpressed HOXA9 induces expansion of the HSC population without disrupting differentiation.
From these results, it appears that HOXA9 is important in maintaining HSC populations, as well as guiding their differentiation, especially towards myeloid (erythroid and granulocyte) lineages.
Throughout the development of a mammal, there are three distinct stages of erythrocyte formation – embryonic, fetal and adult. Adult erythrocytes are the most common blood cell type in mammals, and their characteristic biconcave shape, 7-8 μm diameter and enucleation are amongst the greatest commonalities between mammalian species. However, primitive and fetal erythrocytes, which circulate during early stages of development, are markedly different from their adult counterparts, most obviously through their larger size, shorter lifespan, nucleation, containment of different hemoglobin chains, and higher oxygen affinity. The reasons for and functions of these differences are not well established.
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HOXA9 AI simulator
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HOXA9
Homeobox protein Hox-A9 is a protein that in humans is encoded by the HOXA9 gene.
In vertebrates, the genes encoding the class of transcription factors called homeobox genes are found in clusters named A, B, C, and D on four separate chromosomes. Expression of these proteins is spatially and temporally regulated during embryonic development. This gene is part of the A cluster on chromosome 7 and encodes a DNA-binding transcription factor which may regulate gene expression, morphogenesis, and differentiation. This gene is highly similar to the abdominal-B (Abd-B) gene of Drosophila fly. A specific translocation event which causes a fusion between this gene and the NUP98 gene has been associated with myeloid leukemogenesis.
As HOXA9 dysfunction has been implicated in acute myeloid leukemia, and expression of the gene has been shown to differ markedly between erythrocyte lineages of different stages of development, the gene is of particular interest from a hematopoietic perspective.
As HOXA9 is part of the homeobox family, involved in setting the body plans of animals, it is likely that HOXA9 would display increased expression in cells with higher differentiation potentials. Indeed in the hematopoietic lineage, it has been found that HOXA9 is preferentially expressed in hematopoietic stem cells (HSCs), and is down-regulated as the cell differentiates and matures further.
HOXA9 knockout mice have been shown to develop a reduction in the number of circulating common myeloid progenitor cells, which differentiate into erythroid progenitor cells. The same study indicated that HOXA9 deficiencies specifically affected the granulocyte lineage of the common myeloid progenitor, and it was in HOXA7 knockout mice where the erythroid lineage was affected; however, ErythronDB shows HOXA7 as being insignificantly expressed in all stages of each erythroid lineage. This is something that needs to be investigated further, and could shed light on the interactions between the genes in the HOXA family.
Another study found that HOXA9 knockout HSCs displayed a 5-fold impairment to proliferation rate in vitro, as well as delayed maturation to committed progenitors, specifically myeloid maturation, and that normal proliferation and differentiation rates could be reinstated by reintroducing a HOXA9 vector into the culture. In vivo, lethally irradiated mice with transplanted HOXA9 knockout HSCs displayed a 4-fold to 12-fold reduction in repopulating ability. Furthermore, they developed 60% less myeloid and erythroid colonies in the bone marrow when compared to the wild type. Furthermore, transgenic mice with overexpressed HOXA9 developed a 15-fold increase in the amount of committed progenitor cells in the bone marrow, indicating that overexpressed HOXA9 induces expansion of the HSC population without disrupting differentiation.
From these results, it appears that HOXA9 is important in maintaining HSC populations, as well as guiding their differentiation, especially towards myeloid (erythroid and granulocyte) lineages.
Throughout the development of a mammal, there are three distinct stages of erythrocyte formation – embryonic, fetal and adult. Adult erythrocytes are the most common blood cell type in mammals, and their characteristic biconcave shape, 7-8 μm diameter and enucleation are amongst the greatest commonalities between mammalian species. However, primitive and fetal erythrocytes, which circulate during early stages of development, are markedly different from their adult counterparts, most obviously through their larger size, shorter lifespan, nucleation, containment of different hemoglobin chains, and higher oxygen affinity. The reasons for and functions of these differences are not well established.