Myeloerythroid-restricted progenitors are sufficient to confer radioprotection and provide the majority of day 8 CFU-S

Nakorn, Thanyaphong Na; Traver, David; Weissman, Irving L.; Akashi, Koichi

doi:10.1172/jci15272

Cited by 100 publications

(111 citation statements)

References 38 publications

(5 reference statements)

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“…The fact that not only leukocytes but also erythrocytes and platelets showed accelerated recovery on overexpression of cyclin D2 in hematopoietic progenitor cells was of considerable importance, because recent studies have demonstrated that the ability to rapidly reconstitute these lineages play a key role in rescuing lethally irradiated recipients. 3 This could also explain why G-CSF treatment after transplantation failed to significantly protect mice from lethal irradiation.…”

Section: Discussionmentioning

confidence: 99%

“…3,28 Thus, we next transplanted (CD45.1) LSK cells transduced with control-or cyclin D2-containing vectors together with congenic (CD45.2) competitor cells into lethally irradiated recipients and investigated their ability to rapidly reconstitute mature PB cells. Three to 4 weeks after transplantation, recipients were reconstituted to a considerably higher degree with cyclin D2-transduced than control-transduced cells, both with regard to total ( Figure 3A) and myeloid ( Figure 3B) reconstitution.…”

Section: Cyclin D2 Promotes Rescue Of Lethally Ablated Recipients By mentioning

confidence: 99%

“…1,2 However, LT-HSCs appear less efficient at rapidly reconstituting hematopoiesis on transplantation, and rather distinct populations of short-term HSCs (ST-HSCs) and progenitors are critical for immediate replenishment of short-lived myeloid cells following hematopoietic transplantations. 1,3 Severe and prolonged cytopenias continue to represent a major cause of morbidity and mortality following transplantations. 4 HSCs and progenitors expand during development and on transplantation, 5 and it is, therefore, natural to seek to improve the quality of hematopoietic grafts by ex vivo expansion.…”

Section: Introductionmentioning

confidence: 99%

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Enforced expression of cyclin D2 enhances the proliferative potential of myeloid progenitors, accelerates in vivo myeloid reconstitution, and promotes rescue of mice from lethal myeloablation

Sasaki

Jensen

Karlsson

et al. 2004

Blood

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Section: Discussionmentioning

confidence: 99%

Section: Cyclin D2 Promotes Rescue Of Lethally Ablated Recipients By mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Enforced expression of cyclin D2 enhances the proliferative potential of myeloid progenitors, accelerates in vivo myeloid reconstitution, and promotes rescue of mice from lethal myeloablation

Sasaki

Jensen

Karlsson

et al. 2004

Blood

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“…Stem/progenitor cells present in the marrow of normal mice expresses CD117 50 and are further divided by the CD34 marker, into specific cell subpopulations 51,52 . CD117 expression identifies also stem/progenitor cells in the marrow of mice with the Gata1 low mutation 11,44 .…”

Section: Stem/progenitor Cells From the Marrow And The Blood Of Gata1mentioning

confidence: 99%

Altered SDF-1/CXCR4 axis in patients with primary myelofibrosis and in the Gata1low mouse model of the disease

Migliaccio

Martelli

Verrucci

et al. 2008

Experimental Hematology

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Objective-To assess whether alterations in the SDF-1/CXCR4 occur in patients with primary myelofibrosis (PMF) and in Gata1 low mice, an animal model for myelofibrosis, and whether these abnormalities might account for increased stem/progenitor cell trafficking.Materials and Methods-In the mouse, SDF-1 mRNA levels were assayed in liver, spleen and marrow. SDF-1 protein levels were quantified in plasma and marrow and CXCR4 mRNA and protein levels were evaluated on stem/progenitor cells and megakaryocytes purified from the marrow. SDF-1 protein levels were also evaluated in plasma and in marrow biopsy specimens obtained from normal donors and PMF patients.Results-In Gata1 low mice, the plasma SDF-1 protein was 5-times higher than normal in younger animals. Furthermore, SDF-1 immuno-staining of marrow sections progressively increased with age. Similar abnormalities were observed in PMF patients. In fact, the plasma SDF-1 levels in PMF patients were significantly higher (by 2-fold) than normal (p<0.01) and SDF-1 immuno-staining of marrow biopsiy specimens demonstrated increased SDF-1 deposition in specific areas. In two of the patients, SDF-1 deposition was normalized by curative therapy with allogenic stem cell transplantation. Similarly to what already has been reported for PMF patients, the marrow from Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Gata1 low mice contained fewer CXCR4 pos CD117 pos cells and these cells expressed low levels of CXCR4 mRNA and protein. NIH Public AccessConclusion-Similar abnormalities in the SDF-1/CXCR4 axis are observed in PMF patients and in the Gata1 low mice model of myelofibrosis. We suggest that these abnormalities contribute to the increased stem/progenitor cell trafficking observed in this mouse model as well as patients with PMF.

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“…GMP express the macrophage colony-stimulating factor receptor (M-CSFR) but not the erythropoietin receptor (Epo-R), while the MEP are M-CSFR -Epo-R ϩ . Recent data demonstrate that lethally irradiated mice can be rescued from radiation-induced pancytopenia by infusion of MEP alone (Nakorn et al, 2002). While the recipient animals are not long-term repopulated by the MEP, these committed progenitors differentiate into platelets and red blood cells that support the animals until surviving (radiation-resistant) endogenous hematopoietic stem cells repopulate all of the peripheral blood cell lineages.…”

Section: Methods Of Identifying Hematopoietic Stem and Progenitor Cellsmentioning

confidence: 99%

Blood cell progenitors: Insights into the properties of stem cells

Yöder

2003

Anat. Rec.

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Hematopoiesis is a dynamic process in which eight lineages of mature blood cells are derived from a common stem cell. Great progress has been made in identifying the functionally disparate progenitors that emerge from the stem cell and in elucidating the molecules required for their growth and survival. Further work will be required to understand the molecular mechanisms that regulate commitment of stem and progenitor cells to each stage of progenitor cell development and ultimately into the mature blood cells. Anat Rec Part A 276A: 66 -74, 2004.

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Myeloerythroid-restricted progenitors are sufficient to confer radioprotection and provide the majority of day 8 CFU-S

Cited by 100 publications

References 38 publications

Enforced expression of cyclin D2 enhances the proliferative potential of myeloid progenitors, accelerates in vivo myeloid reconstitution, and promotes rescue of mice from lethal myeloablation

Enforced expression of cyclin D2 enhances the proliferative potential of myeloid progenitors, accelerates in vivo myeloid reconstitution, and promotes rescue of mice from lethal myeloablation

Altered SDF-1/CXCR4 axis in patients with primary myelofibrosis and in the Gata1low mouse model of the disease

Blood cell progenitors: Insights into the properties of stem cells

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