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Contribution Of Tgf-B Signaling To The Pathogenesis Of Myeloproliferative Neoplasms, Juo-Chin Yao
Contribution Of Tgf-B Signaling To The Pathogenesis Of Myeloproliferative Neoplasms, Juo-Chin Yao
Arts & Sciences Electronic Theses and Dissertations
TGF-b expression is increased in most cases of myeloproliferative neoplasms (MPNs); however, its contribution to disease pathogenesis is not well understood. Here, we explore two specific hypotheses. First, we hypothesize that increased TGF-b signaling in mesenchymal stromal cells contributes to the development of myelofibrosis. Second, we hypothesize that Jak2 mutated hematopoietic stem cells (HSCs) are resistant to the growth suppressive effect of TGF-b, conferring a fitness advantage that contributes to their expansion in MPNs and clonal hematopoiesis. To test the first hypothesis, we abrogated TGF-b signaling in mesenchymal stem/progenitor cells by deleting Tgfbr2 using a doxycycline-repressible Osterix-Cre transgene (Osx-Cre), which …