Hematopoietic progenitor cell abnormalities in Hoxc-8 null mutant mice

Satō, Takashi; Tang, Yang; Naot, Yuval; Nardi, Michael A.; Brûlet, Philippe; Bieberich, Charles J.; Takeshita, Kenichi

doi:10.1002/(sici)1097-010x(19990201)283:2<186::aid-jez9>3.0.co;2-0

Cited by 26 publications

(7 citation statements)

References 24 publications

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“…In the in vitro ESC differentiation system, Mll has been shown to be required for hematopoietic development, and its absence to be rescued by ectopic expression of single Hox genes 24 . Presumably due to redundancy among the many Hox gene paralogues, defects in single Hox genes (e.g., HoxA9 , HoxC8 , HoxB6 , HoxA7 , HoxB4 , HoxB3 ) display only modest hematopoietic phenotypes 25–30 …”

Section: Discussionmentioning

confidence: 99%

The Cdx‐Hox Pathway in Hematopoietic Stem Cell Formation from Embryonic Stem Cells

Lengerke

McKinney‐Freeman

Naveiras

et al. 2007

Annals of the New York Academy of Sciences

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Embryonic stem cells (ESCs) differentiated in vitro will yield a multitude of hematopoietic derivatives, yet progenitors displaying true stem cell activity remain difficult to obtain. Possible causes are a biased differentiation to primitive yolk sac-type hematopoiesis, and a variety of developmental or functional deficiencies. Recent studies in the zebrafish have identified the caudal homeobox transcription factors (cdx1/4) and posterior hox genes (hoxa9a, hoxb7a) as key regulators for blood formation during embryonic development. Activation of Cdx and Hox genes during the in vitro differentiation of mouse ESCs followed by co-culture on supportive stromal cells generates ESC-derived hematopoietic stem cells (HSCs) capable of multilineage repopulation of lethally irradiated adult mice. We show here that brief pulses of ectopic Cdx4 or HoxB4 expression are sufficient to enhance hematopoiesis during ESC differentiation, presumably by acting as developmental switches to activate posterior Hox genes. Insights into the role of the Cdx-Hox gene pathway during embryonic hematopoietic development in the zebrafish have allowed us to improve the derivation of repopulating HSCs from murine ESCs.

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Section: Discussionmentioning

confidence: 99%

The Cdx‐Hox Pathway in Hematopoietic Stem Cell Formation from Embryonic Stem Cells

Lengerke

McKinney‐Freeman

Naveiras

et al. 2007

Annals of the New York Academy of Sciences

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“…In general, experimental approaches which modulate the expression of a single HOX gene or a group of HOX genes and monitor the resulting changes in target genes and cellular processes have been informative. In the three knockout mice models that show significant altered haematopoiesis, only the Hoxa9 −/− animals show a reduction in granulocyte and lymphocyte count 56, whereas in Hoxb6 −/− and Hoxc8 −/− the peripheral blood count is normal 69, 72. This resilience attests to the complex and effective regulatory mechanisms that control haematopoiesis in vivo , and emphasizes the limited potential of experimental models in vitro .…”

Section: Hox Genes In Haematopoiesismentioning

confidence: 90%

The pathophysiology of HOX genes and their role in cancer

Grier

Thompson

Kwasniewska

et al. 2005

The Journal of Pathology

281

215

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The HOM-C clustered prototype homeobox genes of Drosophila, and their counterparts, the HOX genes in humans, are highly conserved at the genomic level. These master regulators of development continue to be expressed throughout adulthood in various tissues and organs. The physiological and patho-physiological functions of this network of genes are being avidly pursued within the scientific community, but defined roles for them remain elusive. The order of expression of HOX genes within a cluster is co-ordinated during development, so that the 3 genes are expressed more anteriorly and earlier than the 5 genes.

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“…Hox knock out mouse models demonstrate a role for Hox genes in normal hematopoiesis Clear evidence of a physiologic role for Hox genes in hematopoiesis has been provided by the analysis of the blood-forming organs of mice bearing targeted deletions of specific genes such as Hoxa9 [29-31 • ], Hoxc8 [32], and Hoxb6 [33]. The requirement for different Hox genes at specific stages of hematopoietic development has been further illustrated by the recent analysis of HoxA7 knock out mice, which suggested a role for this gene in megakaryocyte and erythrocyte development [31 • ].…”

Section: Introductionmentioning

confidence: 92%

Hox regulation of normal and leukemic hematopoietic stem cells

Abramovich

Humphries

2005

Current Opinion in Hematology

138

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The identification of Hox genes as HSC regulators has been exploited to develop strategies to efficiently expand HSCs ex vivo, a key step to the success of therapies based on HSC transplantation and the understanding of mechanisms underlying HSC regulation. As leukemia is the result of deregulation of normal HSC development, the elucidation of the role of Hox in the pathobiology of the disease is helping to understand how HSCs self-renew and differentiate, and moreover, should facilitate the development of strategies for the management of leukemia.

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Hematopoietic progenitor cell abnormalities in Hoxc-8 null mutant mice

Cited by 26 publications

References 24 publications

The Cdx‐Hox Pathway in Hematopoietic Stem Cell Formation from Embryonic Stem Cells

The Cdx‐Hox Pathway in Hematopoietic Stem Cell Formation from Embryonic Stem Cells

The pathophysiology of HOX genes and their role in cancer

Hox regulation of normal and leukemic hematopoietic stem cells

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