Megakaryocyte Lineage Biology

Our initial studies indicate that the megakaryocyte lineage is the first hematopoietic lineage to emerge, along with the primitive erythroid and macrophage lineages, in the murine embryo. These embryonic megakaryocytes provide the first circulating platelets, as early as E10.5, which are extremely large in size and with small alpha granules (Tober, Blood 2007). Subsequent studies indicated that Lin28b regulates the fetal program of gene expression in megakaryocytes and platelets, including the perinatal upregulation of P-selectin (Stolla, Blood Adv 2014). More recent collaborative studies with the laboratory of Craig Morrell have focused on functional differences between neonatal and adult mouse platelets, focusing on the upregulation of immune-modulatory genes and functions in adult platelets (Maurya, ATVB 2023; Maurya, Blood 2026). These studies are focused on better understanding the reason that transfusion of adult platelets into human neonates is associated with death, poor neurodevelopmental outcomes, and lung disease. Current studies are also directed at elucidating the contributions of the Flk2-independent pathway of hematopoietic differentiation to circulating platelets, red blood cells and neutrophils, particularly in response to bone marrow injuries including radiation and chemotherapy.

References

• Maurya P, O’Reilly D, Hilt ZT, Livada AC, McGrath KE, Malloy M, Li C, Ture SK, Palis J, Morrell CN. Neonatal platelets induce monocytes to a myeloid derived suppressor cell phenotype. Blood, in press.
• Livada A, McGrath KE, Malloy M, Li C, Ture S, Kingsley PD, Koniski A, Vit L, Nolan K, Mickelsen D, Monette G, Maurya P, Palis J*, Morrell CN*. Long-lived lung megakaryocytes contribute to platelet recovery in thrombocytopenia models. Journal of Clinical Investigation 134(22):e181111, 2024.
• Maurya P, Ture S, Li C, Scheibel K, McGrath KE, Palis J, Morrell C. Transfusion of adult, but not neonatal, platelets promotes monocyte trafficking in neonatal mice. Arteriosclerosis, Thrombosis, and Vascular Biology 43(6):873-885, 2023.
• Pariser DN, Hilt ZT, Ture SK, Blit-Nitko SK, Looney MR, Cleary SJ, Roman-Pagan E, Saunders J III, Georas SN, Veasey J, Madera F, Santos LT, Arne A, Huynh NPT, Livada AC, Guerrero-Martin SM, Lyons C, Metcalf-Pate KA, McGrath KE, Palis J, Morrell CN. Lung megakaryocytes are immune modulatory cells. Journal of Clinical Investigation 131:e137377, 2021.
• Hilt ZT, Pariser DN, Ture SK, Mohan A, Quijada P, Asante AA, Cameron SJ, Sterling JA, Merkel AR, Johanson AL, Jenkins JL, Small EM, McGrath KE, Palis J, Elliott MR, Morrell CN. Platelet-derived 2M regulates monocyte inflammatory responses. JCI Insights pii:122943, 2019.
• Stolla MC, Kingsley PD, Grant R, Koniski A, Vit L, Catherman SC, Fegan KH, McGrath KE, Daley GQ, Palis J. Lin28b regulates age-dependent differences in platelet function. Blood Advances 3:72-82, 2019.
• Niswander LM, Kingsley PD, McGrath KE, Palis J. SDF-1 dynamically regulates megakaryocyte niche occupancy and thrombopoiesis. Blood 124:277-286, 2014.
• Niswander LM, McGrath KE, Kennedy JC, Palis J. Improved quantitative analysis of primary bone marrow megakaryocytes utilizing imaging flow cytometry. Cytometry Part A 85:302-312, 2014.
• Bernard JJ, Seweryniak KE, Koniski AD, Spinelli SL, Blumberg N, Francis CW, Taubman MB, Palis J, Phipps RP. Foxp3 regulates megakaryopoiesis and platelet function. Arteriosclerosis, Thrombosis and Vascular Biology 29:1874-1882, 2009.
• Tober J, Koniski A, McGrath KE, Vemishetti R, Emerson R, de Mesy-Bentley KKL, Waugh R, Palis J. The megakaryocyte lineage originates from hemangioblast precursors and is an integral component both of primitive and definitive hematopoiesis. Blood 109:1433-1441, 2007.