DEK regulates hematopoietic stem engraftment and progenitor cell proliferation

Hal Broxmeyer, Ferdinand Kappes, Nirit Mor-Vaknin, Maureen Legendre, John Kinzfogl, Scott Cooper, Giao Hangoc, David M. Markovitz

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

DEK is a biochemically distinct protein that is generally found in the nucleus, where it is vital to global heterochromatin integrity. However, DEK is also secreted by cells (eg, macrophages) and influences other adjacent cells (eg, acts as a chemoattractant for certain mature blood cells). We hypothesized that DEK may modulate functions of hematopoietic stem (HSCs) and progenitor (HPCs) cells. C57Bl/6 mice were used to demonstrate that absolute numbers and cycling status of HPCs (colony forming unit-granulocyte macrophage [CFU-GM], burst forming unit-erythroid [BFU-E], and colony forming unit-granulocyte erythroid macrophage megakaryocyte [CFU-GEMM]) in bone marrow (BM) and spleen were significantly enhanced in DEK -/- as compared with wild-type (WT) control mice. Moreover, purified recombinant DEK protein inhibited colony formation in vitro by CFU-GM, BFU-E, and CFU-GEMM from WT BM cells and human cord blood (CB) cells in a dose-dependent fashion, demonstrating that DEK plays a negative role in HPC proliferation in vitro and in vivo. Suppression was direct acting as determined by inhibition of proliferation of single isolated CD34 + CB cells in vitro. In contrast, DEK -/- BM cells significantly demonstrated reduced long term competitive and secondary mouse repopulating HSC capacity compared with WT BM cells, demonstrating that DEK positively regulates engrafting capability of self-renewing HSCs. This demonstrates that DEK has potent effects on HSCs, HPCs, and hematopoiesis, information of biological and potential clinical interest.

Original languageEnglish
Pages (from-to)1449-1454
Number of pages6
JournalStem Cells and Development
Volume21
Issue number9
DOIs
StatePublished - Jun 10 2012

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Hematopoietic Stem Cells
Bone Marrow Cells
Myeloid Progenitor Cells
Blood Cells
Granulocyte-Macrophage Progenitor Cells
Cell Proliferation
Fetal Blood
Heterochromatin
Chemotactic Factors
Hematopoiesis
Recombinant Proteins
Stem Cells
Spleen
Bone Marrow
Macrophages
In Vitro Techniques
Proteins

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Hematology

Cite this

Broxmeyer, H., Kappes, F., Mor-Vaknin, N., Legendre, M., Kinzfogl, J., Cooper, S., ... Markovitz, D. M. (2012). DEK regulates hematopoietic stem engraftment and progenitor cell proliferation. Stem Cells and Development, 21(9), 1449-1454. https://doi.org/10.1089/scd.2011.0451

DEK regulates hematopoietic stem engraftment and progenitor cell proliferation. / Broxmeyer, Hal; Kappes, Ferdinand; Mor-Vaknin, Nirit; Legendre, Maureen; Kinzfogl, John; Cooper, Scott; Hangoc, Giao; Markovitz, David M.

In: Stem Cells and Development, Vol. 21, No. 9, 10.06.2012, p. 1449-1454.

Research output: Contribution to journalArticle

Broxmeyer, H, Kappes, F, Mor-Vaknin, N, Legendre, M, Kinzfogl, J, Cooper, S, Hangoc, G & Markovitz, DM 2012, 'DEK regulates hematopoietic stem engraftment and progenitor cell proliferation', Stem Cells and Development, vol. 21, no. 9, pp. 1449-1454. https://doi.org/10.1089/scd.2011.0451
Broxmeyer, Hal ; Kappes, Ferdinand ; Mor-Vaknin, Nirit ; Legendre, Maureen ; Kinzfogl, John ; Cooper, Scott ; Hangoc, Giao ; Markovitz, David M. / DEK regulates hematopoietic stem engraftment and progenitor cell proliferation. In: Stem Cells and Development. 2012 ; Vol. 21, No. 9. pp. 1449-1454.
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