Megakaryopoiesis pathways. The figure extends from the HSC to platelets and offers a combination of the more “classical” pathway, leading to the common megakaryocyte-erythroid progenitor (MEP), and a proposed “direct” route from the HSC. Pathways leading to platelet production are indicated by blue arrows and other pathways by gray arrows. Surface markers of importance are noted in parentheses in red. LT-HSC, long-term HSC; ST-HSC, short-term HSC; Thy1, thymus 1 (“low” indicates low surface antigen and “–” indicates none detectable); Flt3, FMS-like tyrosine kinase 3; EPOR, erythropoietin receptor; CD41, glycoprotein IIb/IIIa or α_IIbβ₃ integrin receptor; G-CSFR, G-CSF receptor; CMP, common myeloid progenitor; ELP, early lymphoid progenitor; GMP, granulocyte/monocyte progenitor; CLP, common lymphoid progenitor.

Assembly of transcription factor complex at a megakaryocyte-specific gene. A schematic representation of the proximal promoter region of a hypothetical megakaryocyte-specific gene modeled after the Itga2b gene. GATA-1 is shown in the middle binding to its known consensus sequence (69) and interacting with FOG-1, Fli-1, and CBFA2 of the RUNX complex (each interaction is indicated by a 2-headed arrow). Fli-1 and CBFA2 bind to their adjacent cognate on the DNA (89, 122), while FOG-1 is recruited through its interactions with the N-terminal zinc finger of GATA-1. In turn, FOG-1 recruits the NuRD complex and other nuclear factors.

Regulation of megakaryopoiesis by cytokines, chemokines, and transcription factors. In the middle panel, a scheme based on the classical pathway of megakaryopoiesis is shown. Cytokines and chemokines that influence that process are shown on the right side as green arrows to indicate the approximate level of development at which they have their influence. Open white areas in arrows indicate levels at which the cytokine is not known to act. Blue text refers to cytokine receptors of significance in megakaryopoiesis. Transcription factors that affect megakaryopoiesis are shown on the left side, and the lilac-colored arrows indicate the approximate point of their influence. Open white areas in arrows indicate levels at which the transcription factor is not known to act. Clinically relevant diseases linked to defects of these regulators are noted in red, italicized text. CFU-GEMM, CFU, granulocyte, erythrocyte, macrophage, megakaryocyte; CFU-EM, CFU, erythrocyte, megakaryocyte; BFU-EM, burst-forming unit, erythrocyte, megakaryocyte; CFU-Meg, CFU, megakaryocyte.