Genomics

Dataset Information

33

Angptl4 is upregulated under inflammatory conditions in the bone marrow of mice, expands myeloid progenitors, and accelerates reconstitution of platelets after myelosuppressive therapy


ABSTRACT: Upon inflammation, myeloid cell generation in the bone marrow (BM) is broadly enhanced by the action of induced cytokines, which are produced locally or at multiple sites throughout the body. Using microarray studies, we show that Angptl4 is a predominantly upregulated cytokine in the BM during systemic inflammatory conditions. Functionally we found recombinant murine Angptl4 (rmAngptl4) to stimulate the proliferation of myeloid CFUs in vitro. Upon repeated in vivo injections, rmAngptl4 increased BM progenitor cell frequency, and this was paralleled by a relative increase in phenotypically defined granulocyte-macrophage progenitors (GMPs). Furthermore, in vivo treatment with rmAngptl4 resulted in elevated platelet counts in steady-state mice and a significantly accelerated reconstitution of platelets in post-transplanted mice after myelosuppressive therapy. In contrast, transplantation of BM cells from donor mice pre-treated with rmAngptl4 had no effect on the recovery of platelets. The administration of rmAngptl4 additionally increased the number of CD61+CD41low-expressing megakaryocytes (MKs) in the BM of steady-state and in the spleen of transplanted mice as well as after in vitro MK-differentiation from hematopoietic stem and progenitor cells. Furthermore, using a stat3 reporter knockin model, we show that rmAngptl4 induces de novo stat3 expression in immature MKs which could be important for the effective expansion of MKs after myelosuppressive therapy. In summary our data suggest that Angptl4 plays a complementary role in hematopoiesis during emergency situations like sepsis. The use of Angptl4 in the setting of autologous stem cell transplantation could represent a potential approach for accelerating the reconstitution of megakaryopoiesis. Overall design: in total 4 probes: 2 replica of BM cells isolated from PBS- and LPS-treated C57BL/6N mice

INSTRUMENT(S): [MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version]

SUBMITTER: Bernd Denecke  

PROVIDER: GSE55161 | GEO | 2017-02-11

SECONDARY ACCESSION(S): PRJNA238662

REPOSITORIES: GEO

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