Developmental changes in human megakaryopoiesis

Abstract

Our analysis of the pattern of TF network and signaling pathways was consistent with a growing specialization of MKs towards hemostasis during ontogeny, and support the idea that MKs derived from hESCs reflect primitive hematopoiesis.

Understanding platelet generation from megakaryocytes: implications for in vitro–derived platelets

“…On average, ;10 to 20 human megakaryocytes/starting stem or progenitor cells are generated in vitro, but of that total number only ;10% to 30% show characteristics of generating platelets as evidenced by proplatelet formation (PPF). 9,27 This number can be increased when cells are cultured in the presence of extracellular matrix proteins, but final platelet yield/ megakaryocyte numbers of ,50 remain far below the estimated 10 3 platelets released from bone marrow-derived megakaryocytes. Each apheresis donor unit contains ;3 3 10 11 platelets making it logistically difficult and prohibitively expensive to generate such numbers without major improvements to the current stem celldifferentiation systems.…”

Inducible Gata1 suppression expands megakaryocyte-erythroid progenitors from embryonic stem cells

“…Alternatively, megakaryocytes from ES cells and fetal tissues are biologically distinct from adult megakaryocytes and their platelet progeny may have inherently reduced life spans (28)(29)(30). Human ES cell-derived megakaryocytes are believed to approximate those derived from early embryonic yolk sacs (31). Whether this is true for G1ME2 cellderived megakaryocytes requires further investigation.…”

Neonatal expression of RNA-binding protein IGF2BP3 regulates the human fetal-adult megakaryocyte transition

“…However, PSC-derived megakaryocytes display poor platelet yields (42), and extensive profiling has shown these cells to be even more ontogenically primitive than human FL megakaryocytes, likely reflecting a yolk-sac stage (10). Thus, ontogenic manipulation has the potential to improve both yield and quality of ex vivo-derived platelets.…”

“…The morphogenetic impairment correlates directly with diminished capacity for platelet release (9). Fetal liver (FL) HSPCs and embryonic stem cell progenitors have even more limited morphogenetic potential than CB HSPCs (10), indicating a graded influence of ontogenic stage. Importantly, the ontogenic influence on megakaryopoiesis, while affecting morphogenesis and proliferation, does not affect all aspects of the megakaryocyte differentiation program (8).…”