An age-progressive platelet differentiation path from hematopoietic stem cells causes exacerbated thrombosis
Year: 2024
Type: article
Abstract: Platelet dysregulation is drastically increased with advanced age and contributes to making cardiovascular disorders the leading cause of death of elderly humans. Here, we reveal a direct differentiation pathway from hematopoietic stem cells into platelets that is progressively propagated upon aging. Remarkably, the aging-enriched platelet path is decoupled from all other hematopoietic lineages, including erythropoiesis, and operates as an additional layer in parallel with canonical platelet production. This results in two molecularly and functionally distinct populations of megakaryocyte progenitors. The age-induced megakaryocyte progenitors have a profoundly enhanced capacity to engraft, expand, restore, and reconstitute platelets in situ and upon transplantation and produce an additional platelet population in old mice. The two pools of co-existing platelets cause age-related thrombocytosis and dramatically increased thrombosis in vivo . Strikingly, aging-enriched platelets are functionally hyper-reactive compared with the canonical platelet populations. These findings reveal stem cell-based aging as a mechanism for platelet dysregulation and age-induced thrombosis.
Source: Cell
Authors: Donna M. Poscablo, Atesh K. Worthington, Stephanie Smith-Berdan, Marcel G.E. Rommel, Bryce A. Manso, Reheman Adili, Lydia Mok, Roman E. Reggiardo, Taylor Cool, Raana Mogharrab, Jenna Myers, Steven Dahmen, Paloma Medina, Anna E. Beaudin, Scott W. Boyer, Michael Holinstat, Vanessa D. Jonsson, E. Camilla Forsberg
Institutions: University of California, Santa Cruz, University of Michigan
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $10,400
Funders: Howard Hughes Medical Institute, California Institute for Regenerative Medicine, American Heart Association, Tobacco-Related Disease Research Program, University of California, Santa Cruz, National Institutes of Health, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: G1144470859, G1416682573, Defining regulators of hematopoietic stem cell self-renewal and lineage potential, G2002586497, G2098138821, G2172073287, G2560966396, CIRM Training Program in Systems Biology of Stem Cells, G3122893257, G3127232634, Defining Cellular and Molecular Mechanisms of the Age-Specific Platelet Pathway, CytoFLEX LX Cell Analyzer, G6628019121, UC Santa Cruz IBSC Facility, G9000047598, G9000157085, G9000279376, Hematopoietic circRNA-mediated intercellular communication
OpenAlex ID: W4396889801