Fanconi anemia type C-deficient hematopoietic stem/progenitor cells exhibit aberrant cell cycle control

Xiaxin Li, P. Artur Plett, Yanzhu Yang, Ping Hong, Brian Freie, Edward Srour, Christie Orschell, D. Clapp, Laura Haneline

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

The pathogenesis of bone marrow failure in Fanconi anemia is poorly understood. Suggested mechanisms include enhanced apoptosis secondary to DNA damage and altered inhibitory cytokine signaling. Recent data determined that disrupted cell cycle control of hematopoietic stem and/or progenitor cells disrupts normal hematopoiesis with increased hematopoietic stem cell cycling resulting in diminished function and increased sensitivity to cell cycle-specific apoptotic stimuli. Here, we used Fanconi anemia complementation type C-deficient (Fancc-/-) mice to demonstrate that Fancc -/- phenotypically defined cell populations enriched for hematopoietic stem and progenitor cells exhibit increased cycling. In addition, we established that the defect in cell cycle regulation is not a compensatory mechanism from enhanced apoptosis occurring in vivo. Collectively, these data provide a previously unrecognized phenotype in Fancc-/- hematopoietic stem/progenitor cells, which may contribute to the progressive bone marrow failure in Fanconi anemia.

Original languageEnglish
Pages (from-to)2081-2084
Number of pages4
JournalBlood
Volume102
Issue number6
DOIs
StatePublished - Sep 15 2003

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Fanconi Anemia
Hematopoietic Stem Cells
Cell Cycle Checkpoints
Stem cells
Cells
Bone
Apoptosis
Cell Cycle
Bone Marrow
Cytokines
Hematopoiesis
Defects
DNA
DNA Damage
Phenotype

ASJC Scopus subject areas

  • Hematology

Cite this

Fanconi anemia type C-deficient hematopoietic stem/progenitor cells exhibit aberrant cell cycle control. / Li, Xiaxin; Plett, P. Artur; Yang, Yanzhu; Hong, Ping; Freie, Brian; Srour, Edward; Orschell, Christie; Clapp, D.; Haneline, Laura.

In: Blood, Vol. 102, No. 6, 15.09.2003, p. 2081-2084.

Research output: Contribution to journalArticle

Li, Xiaxin ; Plett, P. Artur ; Yang, Yanzhu ; Hong, Ping ; Freie, Brian ; Srour, Edward ; Orschell, Christie ; Clapp, D. ; Haneline, Laura. / Fanconi anemia type C-deficient hematopoietic stem/progenitor cells exhibit aberrant cell cycle control. In: Blood. 2003 ; Vol. 102, No. 6. pp. 2081-2084.
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