Analysis of a New Haematopoietic Stem/Progenitor Cells with Megakaryocyte Differentiation Potential

Thrombocytopenia is a common clinical condition and requires more effective treatments. Our previous original work confirmed that 5-HT contributes to the expansion of cord blood stem/progenitor cells (CD34+/CD41+CD61+) and haematopoietic reconstitution in NOD/SCID mice, and through 5-HT2R and Erk1/2 pathway, 5-HT remodel F-actin organization, promoting megakaryocytes to pro-platelet formation (Stem Cells, 2007; 2014). It is suggested that there is a subtype of haematopoietic stem cells (CD34+5HT2R+) with the potential to differentiate into megakaryocytes (CD41+5HT2R+). We studied the specific functions of cells through subsequent experiments, including receptor expression and signaling pathways. Results showed that: (1) The presence of 5-HT2 receptors on CD34+ and CD41+ cells; (2) 5-HT activated the PI3K/AKT pathway and the Wnt/β-catenin pathway via 5-HT2R in CD34+ and CD41+ cells, with anti-apoptotic and pro-proliferative functions; (3) These CD34+5HT2R+ differentiated CD41+5HT2R+ cells, 5-HT acted on 5-HT2R and Erk1/2 pathways, and promoted the formation of pro-platelets by F-actin reorganization; (4) CD34+5HT2R+ haematopoietic stem cells implanted in NOD/SCID mice reconstituted blood function, especially on thrombopoiesis. This study provides a more scientific basis for haematopoiesis and drug development, especially for the treatment of thrombocytopenia.