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Beta-catenin is dispensable for hematopoiesis and lymphopoiesis.

Cobas M, Wilson A, Ernst B, Mancini SJ, MacDonald HR, Kemler R, Radtke F - J. Exp. Med. (2004)

Bottom Line: Beta-catenin-mediated Wnt signaling has been suggested to be critically involved in hematopoietic stem cell maintenance and development of T and B cells in the immune system.Unexpectedly, here we report that inducible Cre-loxP-mediated inactivation of the beta-catenin gene in bone marrow progenitors does not impair their ability to self-renew and reconstitute all hematopoietic lineages (myeloid, erythroid, and lymphoid), even in competitive mixed chimeras.In contrast to earlier reports, these data exclude an essential role for beta-catenin during hematopoiesis and lymphopoiesis.

View Article: PubMed Central - PubMed

Affiliation: Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland.

ABSTRACT
Beta-catenin-mediated Wnt signaling has been suggested to be critically involved in hematopoietic stem cell maintenance and development of T and B cells in the immune system. Unexpectedly, here we report that inducible Cre-loxP-mediated inactivation of the beta-catenin gene in bone marrow progenitors does not impair their ability to self-renew and reconstitute all hematopoietic lineages (myeloid, erythroid, and lymphoid), even in competitive mixed chimeras. In addition, both thymocyte survival and antigen-induced proliferation of peripheral T cells is beta-catenin independent. In contrast to earlier reports, these data exclude an essential role for beta-catenin during hematopoiesis and lymphopoiesis.

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Absence of β-catenin does not affect spontaneous or glucocorticoid-induced death of thymocytes. (a) Percentage of surviving thymocytes gated on CD45.1+ (WT donor) or CD45.2+ (β-catenin−/− donor) derived from mixed BM chimeras after 12 h of culture at 37°C. The percentage of surviving cells is normalized to control cells maintained at 4°C. Data represent mean ± SD of five experiments. (b) Glucocorticoid-induced cell death in WT (CD45.1+) and β-catenin−/− (CD45.2+) CD4+ CD8+ DP thymocytes after 12 h of culture at 37°C. Data are normalized to untreated controls and represent mean ± SD from five individual experiments.
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fig5: Absence of β-catenin does not affect spontaneous or glucocorticoid-induced death of thymocytes. (a) Percentage of surviving thymocytes gated on CD45.1+ (WT donor) or CD45.2+ (β-catenin−/− donor) derived from mixed BM chimeras after 12 h of culture at 37°C. The percentage of surviving cells is normalized to control cells maintained at 4°C. Data represent mean ± SD of five experiments. (b) Glucocorticoid-induced cell death in WT (CD45.1+) and β-catenin−/− (CD45.2+) CD4+ CD8+ DP thymocytes after 12 h of culture at 37°C. Data are normalized to untreated controls and represent mean ± SD from five individual experiments.

Mentions: Because TCF1−/− thymocytes exhibit increased apoptosis probably due to reduced levels of Bcl-xL proteins (30), spontaneous and glucocorticoid-induced cell death of β-catenin–deficient and WT thymocytes were analyzed. Total thymocytes from β-catenin−/− and control BM chimeras were cultured at 37°C in the presence or absence of different concentrations of dexamethasone. The rate of spontaneous apoptosis as well as glucocorticoid-mediated death of DP thymocytes was similar between β-catenin−/− and WT chimeras (Fig. 5) .


Beta-catenin is dispensable for hematopoiesis and lymphopoiesis.

Cobas M, Wilson A, Ernst B, Mancini SJ, MacDonald HR, Kemler R, Radtke F - J. Exp. Med. (2004)

Absence of β-catenin does not affect spontaneous or glucocorticoid-induced death of thymocytes. (a) Percentage of surviving thymocytes gated on CD45.1+ (WT donor) or CD45.2+ (β-catenin−/− donor) derived from mixed BM chimeras after 12 h of culture at 37°C. The percentage of surviving cells is normalized to control cells maintained at 4°C. Data represent mean ± SD of five experiments. (b) Glucocorticoid-induced cell death in WT (CD45.1+) and β-catenin−/− (CD45.2+) CD4+ CD8+ DP thymocytes after 12 h of culture at 37°C. Data are normalized to untreated controls and represent mean ± SD from five individual experiments.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2211763&req=5

fig5: Absence of β-catenin does not affect spontaneous or glucocorticoid-induced death of thymocytes. (a) Percentage of surviving thymocytes gated on CD45.1+ (WT donor) or CD45.2+ (β-catenin−/− donor) derived from mixed BM chimeras after 12 h of culture at 37°C. The percentage of surviving cells is normalized to control cells maintained at 4°C. Data represent mean ± SD of five experiments. (b) Glucocorticoid-induced cell death in WT (CD45.1+) and β-catenin−/− (CD45.2+) CD4+ CD8+ DP thymocytes after 12 h of culture at 37°C. Data are normalized to untreated controls and represent mean ± SD from five individual experiments.
Mentions: Because TCF1−/− thymocytes exhibit increased apoptosis probably due to reduced levels of Bcl-xL proteins (30), spontaneous and glucocorticoid-induced cell death of β-catenin–deficient and WT thymocytes were analyzed. Total thymocytes from β-catenin−/− and control BM chimeras were cultured at 37°C in the presence or absence of different concentrations of dexamethasone. The rate of spontaneous apoptosis as well as glucocorticoid-mediated death of DP thymocytes was similar between β-catenin−/− and WT chimeras (Fig. 5) .

Bottom Line: Beta-catenin-mediated Wnt signaling has been suggested to be critically involved in hematopoietic stem cell maintenance and development of T and B cells in the immune system.Unexpectedly, here we report that inducible Cre-loxP-mediated inactivation of the beta-catenin gene in bone marrow progenitors does not impair their ability to self-renew and reconstitute all hematopoietic lineages (myeloid, erythroid, and lymphoid), even in competitive mixed chimeras.In contrast to earlier reports, these data exclude an essential role for beta-catenin during hematopoiesis and lymphopoiesis.

View Article: PubMed Central - PubMed

Affiliation: Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland.

ABSTRACT
Beta-catenin-mediated Wnt signaling has been suggested to be critically involved in hematopoietic stem cell maintenance and development of T and B cells in the immune system. Unexpectedly, here we report that inducible Cre-loxP-mediated inactivation of the beta-catenin gene in bone marrow progenitors does not impair their ability to self-renew and reconstitute all hematopoietic lineages (myeloid, erythroid, and lymphoid), even in competitive mixed chimeras. In addition, both thymocyte survival and antigen-induced proliferation of peripheral T cells is beta-catenin independent. In contrast to earlier reports, these data exclude an essential role for beta-catenin during hematopoiesis and lymphopoiesis.

Show MeSH
Related in: MedlinePlus