Role of Chk1 in the differentiation program of hematopoietic stem cells

被引：7

作者：

Carrassa, Laura ^{[1
]}

Montelatici, Elisa ^{[2
]}

Lazzari, Lorenza ^{[2
]}

Zangrossi, Stefano ^{[2
]}

Simone, Matteo ^{[1
]}

Broggini, Massimo ^{[1
]}

Damia, Giovanna ^{[1
]}

机构：

[1] Ist Ric Farmacol Mario Negri, Dept Oncol, Mol Pharmacol Lab, I-20156 Milan, Italy

[2] Osped Maggiore Policlin, Dept Regenerat Med, Ctr Transfus Med Cell Therapy & Cryobiol, Milan, Italy

来源：

CELLULAR AND MOLECULAR LIFE SCIENCES | 2010年 / 67卷 / 10期

关键词：

Stem and progenitor cells; Umbilical cord blood; Chk1; DNA damage; Differentiation; UMBILICAL-CORD BLOOD; DNA-DAMAGE RESPONSE; CHECKPOINT FUNCTION; SPINDLE CHECKPOINT; STRESS RESPONSES; PROGENITOR CELLS; DOWN-REGULATION; IN-VIVO; KINASE; ATR;

D O I：

10.1007/s00018-010-0274-1

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Hematopoietic stem cells (HSC) isolated from umbilical cord blood (UCB) were treated with ionizing radiation (IR) and sensitivity and IR induced checkpoints activation were investigated. No difference in the sensitivity and in the activation of DNA damage pathways was observed between CD133+ HSC and cells derived from them after ex vivo expansion. Chk1 protein was very low in freshly isolated CD133+ cells, and undetectable in ex vivo expanded UCB CD133+ cells. Chk1 was expressed only on day 3 of the ex vivo expansion. This pattern of Chk1 expression was corroborated in CD133+ cells isolated from peripheral blood apheresis collected from an healthy donor. Treatment with a specific Chk1 inhibitor resulted in a strong reduction in the percentage of myeloid precursors (CD33+) and an increase in the percentage of lymphoid precursors (CD38+) compared to untreated cells, suggesting a possible role for Chk1 in the differentiation program of UCB CD133+ HSC.

引用

页码：1713 / 1722

页数：10

共 39 条

[1] ES cells do not activate p53-dependent stress responses and undergo p53-independent apoptosis in response to DNA damage [J].

Aladjem, MI ;

Spike, BT ;

Rodewald, LW ;

Hope, TJ ;

Klemm, M ;

Jaenisch, R ;

Wahl, GM .

CURRENT BIOLOGY, 1998, 8 (03) :145-155

[2] Initiating cellular stress responses [J].

Bakkenist, CJ ;

Kastan, MB .

CELL, 2004, 118 (01) :9-17

[3] Chk1 and Chk2 kinases in checkpoint control and cancer [J].

Bartek, J ;

Lukas, J .

CANCER CELL, 2003, 3 (05) :421-429

[4] Stringent regulation of DNA repair during human hematopoietic differentiation: A gene expression and functional analysis [J].

Bracker, Tomke U. ;

Giebel, Bernd ;

Spanholtz, Jan ;

Sorg, Ursula R. ;

Klein-Hitpass, Ludger ;

Moritz, Thomas ;

Thomale, Juergen .

STEM CELLS, 2006, 24 (03) :722-730

[5] Cord blood transplantation for adults [J].

Brunstein, Claudio G. ;

Wagner, John E. .

VOX SANGUINIS, 2006, 91 (03) :195-205

[6] Hematopoietic stem cells - The paradigmatic tissue-specific stem cell [J].

Bryder, David ;

Rossi, Derrick J. ;

Weissman, Irving L. .

AMERICAN JOURNAL OF PATHOLOGY, 2006, 169 (02) :338-346

[7] Down-regulation of DNA repair in human CD34+ progenitor cells corresponds to increased drug sensitivity and apoptotic response [J].

Buschfort-Papewalis, C ;

Moritz, T ;

Liedert, B ;

Thomale, J .

BLOOD, 2002, 100 (03) :845-853

[8]

Carrassa L, 2004, CELL CYCLE, V3, P1177

[9]

Carrassa L, 2009, J CELL MOL MED, V13, P1565, DOI 10.1111/j.1582-4934.2009.00362.x

[10] Activation of DNA damage response signaling in mouse embryonic stem cells [J].

Chuykin, Ilya A. ;

Lianguzova, Maria S. ;

Pospelova, Tatiana V. ;

Pospelov, Valery A. .

CELL CYCLE, 2008, 7 (18) :2922-2928

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