Browsing by Subject "c-Kit"

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    Hematopoietic Stem Cell Identification Postirradiation
    (Springer, 2023) Patterson, Andrea M.; Orschell, Christie M.; Pelus, Louis M.; Medicine, School of Medicine
    Radiation exposure is particularly damaging to cells of the hematopoietic system, inducing pancytopenia and bone marrow failure. The study of these processes, as well as the development of treatments to prevent hematopoietic damage or enhance recovery after radiation exposure, often require analysis of bone marrow cells early after irradiation. While flow cytometry methods are well characterized for identification and analysis of bone marrow populations in the nonirradiated setting, multiple complications arise when dealing with irradiated tissues. Among these complications is a radiation-induced loss of c-Kit, a central marker for conventional gating of primitive hematopoietic populations in mice. These include hematopoietic stem cells (HSCs), which are central to blood reconstitution and life-long bone marrow function, and are important targets of analysis in these studies. This chapter outlines techniques for HSC identification and analysis from mouse bone marrow postirradiation.
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    Protein Tyrosine Phosphatase PRL2 Mediates Notch and Kit Signals in Early T Cell Progenitors
    (Wiley, 2017-04) Kobayashi, Michihiro; Nabinger, Sarah; Bai, Yunpeng; Yoshimoto, Momoko; Gao, Rui; Chen, Sisi; Yao, Chonghua; Dong, Yuanshu; Zhang, Lujuan; Rodriguez, Sonia; Yashiro- Ohtan, Yumi; Pear, Warren S.; Carlesso, Nadia; Yoder, Mervin C.; Kapur, Reuben; Kaplan, Mark H.; Lacorazza, H. Daniel; Zhang, Zhong-Yin; Liu, Yan; Pediatrics, School of Medicine
    The molecular pathways regulating lymphoid priming, fate, and development of multipotent bone marrow hematopoietic stem and progenitor cells (HSPCs) that continuously feed thymic progenitors remain largely unknown. While Notch signal is indispensable for T cell specification and differentiation, the downstream effectors are not well understood. PRL2, a protein tyrosine phosphatase that regulates hematopoietic stem cell proliferation and self-renewal, is highly expressed in murine thymocyte progenitors. Here we demonstrate that protein tyrosine phosphatase PRL2 and receptor tyrosine kinase c-Kit are critical downstream targets and effectors of the canonical Notch/RBPJ pathway in early T cell progenitors. While PRL2 deficiency resulted in moderate defects of thymopoiesis in the steady state, de novo generation of T cells from Prl2 null hematopoietic stem cells was significantly reduced following transplantation. Prl2 null HSPCs also showed impaired T cell differentiation in vitro. We found that Notch/RBPJ signaling upregulated PRL2 as well as c-Kit expression in T cell progenitors. Further, PRL2 sustains Notch-mediated c-Kit expression and enhances stem cell factor/c-Kit signaling in T cell progenitors, promoting effective DN1-DN2 transition. Thus, we have identified a critical role for PRL2 phosphatase in mediating Notch and c-Kit signals in early T cell progenitors.