Wnt3a Activates Dormant c-Kit− Bone Marrow-Derived Cells with Short-Term Multilineage Hematopoietic Reconstitution Capacity
العنوان: | Wnt3a Activates Dormant c-Kit− Bone Marrow-Derived Cells with Short-Term Multilineage Hematopoietic Reconstitution Capacity |
---|---|
المؤلفون: | Mickie Bhatia, Borhane Guezguez, Randall T. Moon, Jennifer J. Trowbridge |
المصدر: | Stem Cells. 28:1379-1389 |
بيانات النشر: | Oxford University Press (OUP), 2010. |
سنة النشر: | 2010 |
مصطلحات موضوعية: | Myeloid, Cellular differentiation, Population, Bone Marrow Cells, Mice, SCID, Biology, Polymerase Chain Reaction, Wnt3 Protein, Mice, Mice, Inbred NOD, Pregnancy, Wnt3A Protein, medicine, Animals, Progenitor cell, education, Cells, Cultured, education.field_of_study, Cell Cycle, Hematopoietic Stem Cell Transplantation, Wnt signaling pathway, Cell Differentiation, Cell Biology, Hematopoietic Stem Cells, Mice, Inbred C57BL, Wnt Proteins, Proto-Oncogene Proteins c-kit, Haematopoiesis, medicine.anatomical_structure, Liver, Cancer research, Molecular Medicine, Female, Bone marrow, Stem cell, Signal Transduction, Developmental Biology |
الوصف: | Quiescent cells lacking expression of mature lineage makers and the c-Kit receptor reside in adult bone marrow. Despite their phenotypic similarity to hematopoietic stem cells, these Lin−Sca-1+c-Kit− cells lack myeloid and erythroid potential and long-term hematopoietic repopulating capacity, whereas, recent studies have functionally demonstrated that the Lin−Sca-1+c-Kit− population contains early lymphoid-committed progenitors. Examining the role of Wnt signaling in regulation of this population, we found that c-Kit− cells express diverse Wnt receptors and proliferate upon Wnt pathway activation in vitro and in vivo. Stimulation with Wnt3a, but not Wnt5a or Wnt11, promoted c-Kit− cells to give rise to myeloid and erythroid progenitors with robust self-renewal capacity measured by clonal replating. In addition, Wnt3a-stimulated c-Kit− cells gave rise to all hematopoietic lineages (lymphoid, myeloid, and erythroid) upon transplant into the liver of newborn recipient mice. Our study reveals that Wnt3a activates unique cell fate decisions of dormant c-Kit− that promotes short-term multilineage reconstitution capacity in vivo, thereby revealing a unique role for Wnt activation in hematopoiesis. Overall, our results highlight the potential of utilizing signaling molecules known to have instructive roles in regeneration to discover cell subsets residing in adult organisms with unexploited regenerative capacity. |
تدمد: | 1549-4918 1066-5099 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d2e2da89608e824a3a1ce0ef0df2152e https://doi.org/10.1002/stem.457 |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi.dedup.....d2e2da89608e824a3a1ce0ef0df2152e |
قاعدة البيانات: | OpenAIRE |
تدمد: | 15494918 10665099 |
---|