Lin28b Reprograms Adult Bone Marrow Hematopoietic Progenitors to Mediate Fetal-Like Lymphopoiesis

• Published in: Science (American Association for the Advancement of Science) Vol. 335; no. 6073; pp. 1195 - 1200
• Main Authors: Yuan, Joan, Nguyen, Cuong K., Liu, Xiuhuai, Kanellopoulou, Chrysi, Muljo, Stefan A.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 09.03.2012; The American Association for the Advancement of Science
• Subjects: Adult stem cells; Adult Stem Cells - physiology; Adults; Animals; B-Lymphocyte Subsets - cytology; B-Lymphocyte Subsets - immunology; B-Lymphocyte Subsets - physiology; B-Lymphocytes - cytology; B-Lymphocytes - physiology; Biological and medical sciences; Bone marrow; Bone Marrow Cells - metabolism; Cell Lineage; Cell lines; Cells; Chimeras; Developmental biology; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Fetal Blood - cytology; Fetus; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene expression; Hematopoietic Stem Cells - physiology; Humans; Immune system; Immunobiology; Individualized Instruction; Liver - embryology; Liver - metabolism; Lymphocytes; Lymphoid organs: ontogeny, organization, homing phenomenon; Lymphopoiesis; Mice; Mice, Inbred C57BL; MicroRNA; MicroRNAs - genetics; MicroRNAs - metabolism; Natural killer T cells; Natural Killer T-Cells - cytology; Natural Killer T-Cells - immunology; Natural Killer T-Cells - physiology; RESEARCH ARTICLE; Reverse Transcriptase Polymerase Chain Reaction; RNA-Binding Proteins; T lymphocytes; T-Lymphocyte Subsets - cytology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - physiology; T-Lymphocytes - cytology; T-Lymphocytes - physiology; Thymocytes; Thymus Gland - embryology; Thymus Gland - metabolism; Transduction, Genetic; Human; Lymphopoiesis; Stem cell; Rodentia; Hematopoietic cell; Vertebrata; Mammalia; Gene; Mouse; Cell reprogramming; Hematopoiesis; Adult animal; Bone marrow; Genetics; Progenitor cell
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1216557

The immune system develops in waves during ontogeny; it is initially populated by cells generated from fetal hematopoietic stem cells (HSCs) and later by cells derived from adult HSCs. Remarkably, the genetic programs that control these two distinct stem cell fates remain poorly understood. We report that Lin28b is specifically expressed in mouse and human fetal liver and thymus, but not in adult bone marrow or thymus. We demonstrate that ectopic expression of Lin28 reprograms hematopoietic stem/progenitor cells (HSPCs) from adult bone marrow, which endows them with the ability to mediate multilineage reconstitution that resembles fetal lymphopoiesis, including increased development of B-1a, marginal zone B, gamma/delta (γδ) T cells, and natural killer T (NKT) cells.