Abstract

Prof. harvey F. Lodish, Member, Whitehead Institute for Biomedical Research and Professor of Biology and Bioengineering, Massachusetts Institute of Technology, U.S.A.

Hematopoietic stem cells (HSCs) generate all types of blood cells, including red cells and all cells of the immune system. HSCs undergo self-renewal; the number of HSCs increases during embryogenesis and remains at a steady- state level in adult mammals but can increase in response to stress. Self- renewal of HSCs requires multiple growth factors, including several that we identified.

Formation of red cells from HSCs involves multiple cellular stages: multipotent myeloid progenitors; early erythroid- specific progenitors called a Burst- Forming Units- Erythroid (BFU-E) that respond to several growth factors but not Erythropoietin (Epo); and finally an Epo- responsive progenitor that in three days generates ~30 red cells. I will focus on regulation of BFU-E proliferation and formation of CFU-Es, since our very recent work showed how glucocorticoids stress hormones stimulate red cell production. They allow ~10 times more CFU-Es to be formed from each BFU-E. More specifically, corticosteroids maintain progenitor immaturity during cell division of BFU-E daughter cells, allowing over time increased numbers of divisions of individual BFU-E cells and thus increased numbers of CFU-E cells formed from each BFU-E. This explains why certain corticosteroids are useful in treating certain non- Epo responsive anemias.

Host: Prof. WanJin Hong