Research Article

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

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Science  09 Mar 2012:
Vol. 335, Issue 6073, pp. 1195-1200
DOI: 10.1126/science.1216557

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Making Immune Cells Young Again

Hematopoiesis, the development of the immune system, occurs in distinct waves. The immune system is first populated by cells that arise from fetal hematopoietic stem cells (HSCs) and then later by cells derived from adult HSCs. Furthermore, fetal HSCs give rise to lymphocytes with innate immunelike properties, whereas adult HSCs give rise to classical T and B cells. Yuan et al. (p. 1195, published online 16 February) now uncover the molecular mechanism behind these distinct waves of hematopoiesis. Expression of the RNA binding proteins Lin28 and Lin28b is enriched in fetal hematopoietic stem/progenitor cells (HSPCs) in mice and humans. Ectopic expression of Lin28 in mouse adult HSPCs was sufficient to induce the differentiation of both classical and innate-like lymphocyte lineages.

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.

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