Schematic showing the newly identified differentiation stages in human megakaryopoiesis. (A) Immature low granular (LG) megakaryocytes (MKs) have low ploidy and few α granules. (B) These LG MKs mature in high granular (HG)/CD42b⁺ MKs characterized by increased ploidy, RNA, and α granule content. (C) Mature HG/CD42b⁺ MKs internalize factor V (FV) into their α granules and release FV-labeled platelets. The FV-labeled platelets are similar in size or larger than human donor platelets. (D) Pharmacological inhibition of CD42b shedding from MKs does not prevent apoptosis or improve MK functionality. (E) However, pharmacological inhibition of apoptosis increases the number of CD42b⁺/FV⁺ MKs that release functional platelets. The figure has been adapted from Figure 7 in the article by Sim et al that begins on page 192.