生命学院学术报告

题目：Self-renewal of human hematopoietic progenitor cells: From the clinic to the laboratory and back to the clinic

报告人：Sherry Lee, Ph.D.

Postdoc Fellow, Whitehead Institute for Biomedical Research

时间：4月21日15:30

地点：新生物楼411

Many acute and chronic anemias, including hemolysis, sepsis and genetic bone marrow failure diseases, are not treatable with erythropoietin (Epo), because the colony-forming unit erythroid progenitors (CFU-Es) that respond to Epo are either too few in number or are not sensitive enough to Epo to maintain sufficient red blood cell production. Treatment of these anemias requires a drug that acts at an earlier stage of red cell formation and enhances the formation of Epo-sensitive CFU-E progenitors. In this seminar, I will discuss how potential therapeutic strategies emerge from my studies investigating molecular basis underlying burst-forming unit erythroid progenitors (BFU-Es) self-renewal. My recent study revealed that activation of the peroxisome proliferator-activated receptor α (PPAR-α) by PPAR-α agonists synergizes with the glucocorticoid receptor (GR) to promote BFU-E self-renewal. Over time these agonists significantly increase production of mature red blood cells in both mouse and human primary erythroid cultures, and alleviate anemia in mouse models. I have also demonstrated that PPAR-α cooperates with GR on many chromatin sites to promote BFU-E self-renewal. Furthermore, I have dissected the heterogeneity of BFU-Es by single-cell transcriptome analysis, and uncovered that the type III TGFβ receptor (TGFβ RIII) is a potential marker to distinguish “early” and “late” BFU-Es. The TGFBR3low BFU-E population presumably represents earlier BFU-Es with maximal capacity for self-renewal. Manipulation of TGFβ signaling by TGFβ inhibitors increases TGFBR3low BFU-E cells self-renewal and total erythroblast production. In summary, my studies addressed novel mechanisms underlying erythroid progenitor self-renewal, and provided insights into cell fate decisions of stem and progenitor cells under different environmental conditions. These findings might also lead to the development of new therapies for Epo-untreatable anemias.

欢迎各位老师同学积极参加！