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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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Normal development of β-catenin−/− hematopoietic lineages in a competitive situation. Mixed BM chimeric mice were analyzed 4–6 mo after reconstitution with a 1:2 mixture of WT (CD45.1+) and either β-cateninlox/lox or β-catenin−/− (CD45.2+) BM-derived populations. (a) A representative FACS® analysis of BM stained with anti-CD117 and anti-Sca1 gated on lin− CD45.2+ donor cells of either β-cateninlox/lox or β-catenin−/− mixed chimeras. Numbers indicate relative percentage of HSCs (CD117+ Sca1+) CLPs (CD117low Sca1low), and CMPs (CD117+ Sca1−) in each indicated region. (b) Percentage HSCs, CMPs, and CLPs gated on lin− CD45.2+ cells from either β-cateninlox/lox (open bars) or β-catenin−/− mixed chimeras (shaded bars). The bars represent mean ± SD (n = 8). (c) Percentage early erythroblasts (Ter119+), granulocytes (Gr1+), and macrophages (Gr1− CD11b+) after gating on CD45.2+ cells from either β-cateninlox/lox or β-catenin−/− mixed chimeras. The bars represent mean ± SD (n = 8).
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fig3: Normal development of β-catenin−/− hematopoietic lineages in a competitive situation. Mixed BM chimeric mice were analyzed 4–6 mo after reconstitution with a 1:2 mixture of WT (CD45.1+) and either β-cateninlox/lox or β-catenin−/− (CD45.2+) BM-derived populations. (a) A representative FACS® analysis of BM stained with anti-CD117 and anti-Sca1 gated on lin− CD45.2+ donor cells of either β-cateninlox/lox or β-catenin−/− mixed chimeras. Numbers indicate relative percentage of HSCs (CD117+ Sca1+) CLPs (CD117low Sca1low), and CMPs (CD117+ Sca1−) in each indicated region. (b) Percentage HSCs, CMPs, and CLPs gated on lin− CD45.2+ cells from either β-cateninlox/lox (open bars) or β-catenin−/− mixed chimeras (shaded bars). The bars represent mean ± SD (n = 8). (c) Percentage early erythroblasts (Ter119+), granulocytes (Gr1+), and macrophages (Gr1− CD11b+) after gating on CD45.2+ cells from either β-cateninlox/lox or β-catenin−/− mixed chimeras. The bars represent mean ± SD (n = 8).

Mentions: Surprisingly, the relative number of cells in phenotypically defined progenitor subsets including HSC (lin− CD117+ Sca1+), common myeloid progenitor (CMP; lin− CD117+ Sca1−), and common lymphoid progenitor (CLP; lin− CD117lo Sca1lo Il7Rα+) within donor-derived BM was similar in both control and β-catenin–deficient chimeras (Fig. 3 , a and b). Furthermore, no differences were observed in the percentages of more mature BM cell types (including early erythroblasts, granulocytes, and macrophages) in β-catenin−/− chimeras versus control (Fig. 3 c). The results indicate that β-catenin–deficient BM progenitors can self-renew and differentiate normally in the BM, even in a competitive situation.


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)

Normal development of β-catenin−/− hematopoietic lineages in a competitive situation. Mixed BM chimeric mice were analyzed 4–6 mo after reconstitution with a 1:2 mixture of WT (CD45.1+) and either β-cateninlox/lox or β-catenin−/− (CD45.2+) BM-derived populations. (a) A representative FACS® analysis of BM stained with anti-CD117 and anti-Sca1 gated on lin− CD45.2+ donor cells of either β-cateninlox/lox or β-catenin−/− mixed chimeras. Numbers indicate relative percentage of HSCs (CD117+ Sca1+) CLPs (CD117low Sca1low), and CMPs (CD117+ Sca1−) in each indicated region. (b) Percentage HSCs, CMPs, and CLPs gated on lin− CD45.2+ cells from either β-cateninlox/lox (open bars) or β-catenin−/− mixed chimeras (shaded bars). The bars represent mean ± SD (n = 8). (c) Percentage early erythroblasts (Ter119+), granulocytes (Gr1+), and macrophages (Gr1− CD11b+) after gating on CD45.2+ cells from either β-cateninlox/lox or β-catenin−/− mixed chimeras. The bars represent mean ± SD (n = 8).
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Related In: Results  -  Collection

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

fig3: Normal development of β-catenin−/− hematopoietic lineages in a competitive situation. Mixed BM chimeric mice were analyzed 4–6 mo after reconstitution with a 1:2 mixture of WT (CD45.1+) and either β-cateninlox/lox or β-catenin−/− (CD45.2+) BM-derived populations. (a) A representative FACS® analysis of BM stained with anti-CD117 and anti-Sca1 gated on lin− CD45.2+ donor cells of either β-cateninlox/lox or β-catenin−/− mixed chimeras. Numbers indicate relative percentage of HSCs (CD117+ Sca1+) CLPs (CD117low Sca1low), and CMPs (CD117+ Sca1−) in each indicated region. (b) Percentage HSCs, CMPs, and CLPs gated on lin− CD45.2+ cells from either β-cateninlox/lox (open bars) or β-catenin−/− mixed chimeras (shaded bars). The bars represent mean ± SD (n = 8). (c) Percentage early erythroblasts (Ter119+), granulocytes (Gr1+), and macrophages (Gr1− CD11b+) after gating on CD45.2+ cells from either β-cateninlox/lox or β-catenin−/− mixed chimeras. The bars represent mean ± SD (n = 8).
Mentions: Surprisingly, the relative number of cells in phenotypically defined progenitor subsets including HSC (lin− CD117+ Sca1+), common myeloid progenitor (CMP; lin− CD117+ Sca1−), and common lymphoid progenitor (CLP; lin− CD117lo Sca1lo Il7Rα+) within donor-derived BM was similar in both control and β-catenin–deficient chimeras (Fig. 3 , a and b). Furthermore, no differences were observed in the percentages of more mature BM cell types (including early erythroblasts, granulocytes, and macrophages) in β-catenin−/− chimeras versus control (Fig. 3 c). The results indicate that β-catenin–deficient BM progenitors can self-renew and differentiate normally in the BM, even in a competitive situation.

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