Research Article

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

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Science  16 Feb 2012:
1216557
DOI: 10.1126/science.1216557

Abstract

The immune system develops in waves during ontogeny, being 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 from adult bone marrow, endowing 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 cells.