Abstract
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.
Publication types
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Research Support, N.I.H., Intramural
MeSH terms
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Adult Stem Cells / physiology*
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Animals
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B-Lymphocyte Subsets / cytology
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B-Lymphocyte Subsets / immunology
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B-Lymphocyte Subsets / physiology
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B-Lymphocytes / cytology
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B-Lymphocytes / physiology*
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Bone Marrow Cells / metabolism
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Cell Lineage
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Fetal Blood / cytology
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Fetus
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Flow Cytometry
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Hematopoietic Stem Cells / physiology*
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Humans
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Liver / embryology
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Liver / metabolism
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Lymphopoiesis*
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Mice
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Mice, Inbred C57BL
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MicroRNAs / genetics
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MicroRNAs / metabolism
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Natural Killer T-Cells / cytology
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Natural Killer T-Cells / immunology
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Natural Killer T-Cells / physiology
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RNA-Binding Proteins
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Reverse Transcriptase Polymerase Chain Reaction
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T-Lymphocyte Subsets / cytology
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / physiology
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T-Lymphocytes / cytology
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T-Lymphocytes / physiology*
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Thymus Gland / embryology
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Thymus Gland / metabolism
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Transduction, Genetic
Substances
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DNA-Binding Proteins
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LIN28B protein, human
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Lin28b protein, mouse
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MicroRNAs
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RNA-Binding Proteins
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mirnlet7 microRNA, human
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mirnlet7 microRNA, mouse
Associated data
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GEO/GSE34854
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GEO/GSE35081
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GEO/GSE35107