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Engineering Monocytes: Guiding Murine Myeloid Progenitor Cell Lines Towards the Monocyte Lineage

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Abstract:
Monocytes, white blood cells derived from the myeloid lineage in the bone marrow, are notable for their ability to transform into macrophages or dendritic cells when they migrate into tissues. As those effector cell types, they engulf and digest foreign substances, dead cells, and debris to maintain tissue integrity and initiate immune responses.The Lefort Lab has previously developed a conditionally-immortalized murine myeloid progenitor cell line in which the HoxB8 transcription factor is conditionally upregulated to block the cells’ maturation and differentiation. When transplanted into mice, these cells have been shown to differentiate almost exclusively into mature neutrophils, another innate immune cell type. We hypothesize that our myeloid progenitors are conditionally immortalized in a granulocyte-monocyte progenitor state, with potential to differentiate into monocytes as well as granulocytes.The goals of this study are (i) to assess whether our myeloid progenitors have potential to differentiate into monocytes and (ii) to engineer a monocyte-restricted progenitor line from our multipotent myeloid progenitor line. Preliminary results show that our myeloid progenitors, when introduced to macrophage colony-stimulating factor media, can differentiate into ~10-17% monocytes.Then, knockout three target proteins in our myeloid progenitors (Gfi1, ELANE, and Cebpa) that act as transcriptional factors or repressors important for neutrophil differentiation, which we hypothesize will enhance progenitor differentiation toward the monocyte lineage to produce a monocyte progenitor line. Generating a monocyte progenitor line is beneficial for in vitro and in vivo studies of monocyte function, and could be developed eventually as a cellular therapy for patients with monocytopenia or with macrophage dysfunction.

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Citation

Demetria Tolbert, and Martisen, Melanie, "Engineering Monocytes: Guiding Murine Myeloid Progenitor Cell Lines Towards the Monocyte Lineage" (2024). The Leadership Alliance Digital Library, Summer Research Symposium. Brown Digital Repository. Brown University Library. https://doi.org/10.26300/nnj2-vz40

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  • The Leadership Alliance Digital Library

    A collection of research presentations and posters created by students participating in the Leadership Alliance's Summer Research - Early Identification Program.

    When using this resource, please cite the digital object identifier (DOI) for the specific resource as well as the …

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  • Summer Research Symposium

    Each year, Brown University showcases the research of its undergraduates at the Summer Research Symposium. More than half of the student-researchers are UTRA recipients, while others receive funding from a variety of Brown-administered and national programs and fellowships and go …
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