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Mon, Nov 29, 2021


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12:00pm
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1:00pm
SERIOUS BACTERIAL INFECTION AND THE HEMATOPOIETIC STEM CELL RESPONSE  (Conferences / Seminars / Lectures)

In response to serious bacterial infection, the bone marrow hematopoietic activity shifts toward granulocyte production, which is critical for host defense. At the present time, knowledge about the commitment of hematopoietic precursor cells including hematopoietic stem cells and progenitors in this response remains scant. Our recent studies have shown that bacteremia causes a marked increase in the number of hematopoietic stem cells bearing the lineage (lin)-c-kit+Sca-1+ (LKS) surface markers in the bone marrow of mice. This dramatic expansion of the LKS cell pool results from both increased mitosis of these cells and inversion from lin-c-kit+Sca-1- cell phenotype. TLR4-JNK-AP1 signaling plays a major role in mediating phenotypic inversion of lin-c-kit+Sca-1- cells. Cells in the expanded LKS cell pool are transcriptionally reprogrammed for enhancing their commitment to myeloid lineage development. These primitive precursors contain an increased number of colony-forming unit-granulocyte/macrophage (CFU-GM). Mobilization of LKS cells into the circulation is significantly increased during bacteremia. Kidney capsule implantation test shows that LKS cells generated from inversion of lin-c-kit+Sca-1- cells following LPS stimulation possess a strong activity of extramedullary granulopoiesis. These results demonstrate that the lin-c-kit+Sca-1+ cell population in the bone marrow constitutes a key component of the host defense response to bacteremia. Functional modifications of these primitive hematopoietic precursors are critical for enhancing granulocyte production following bacterial infection.

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Location: B448-449 Life Sciences Building [map]
Price: free
Sponsor: Administration
Contact: Diane Hummel
email pic phm@msu.edu
phone pic (517) 353-9616