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Science 335 (6073): 1195-1200

Copyright © 2012 by the American Association for the Advancement of Science

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

Joan Yuan, Cuong K. Nguyen, Xiuhuai Liu, Chrysi Kanellopoulou, Stefan A. Muljo*

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 ({gamma}{delta}) T cells, and natural killer T (NKT) cells.

Laboratory of Immunology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD 20892, USA.

* To whom correspondence should be addressed. E-mail: stefan.muljo{at}nih.gov


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