Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

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

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
The calcineurin-NFAT pathway negatively regulates megakaryopoiesis.
A. Zaslavsky, S. T. Chou, K. Schadler, A. Lieberman, M. Pimkin, Y. J. Kim, K.-H. Baek, W. C. Aird, M. J. Weiss, and S. Ryeom (2013)
Blood 121, 3205-3215
   Abstract »    Full Text »    PDF »
The Tec Kinase ITK Regulates Thymic Expansion, Emigration, and Maturation of {gamma}{delta} NKT Cells.
C. C. Yin, O. H. Cho, K. E. Sylvia, K. Narayan, A. L. Prince, J. W. Evans, J. Kang, and L. J. Berg (2013)
J. Immunol. 190, 2659-2669
   Abstract »    Full Text »    PDF »
Inactivation of ribosomal protein L22 promotes transformation by induction of the stemness factor, Lin28B.
S. Rao, S.-Y. Lee, A. Gutierrez, J. Perrigoue, R. J. Thapa, Z. Tu, J. R. Jeffers, M. Rhodes, S. Anderson, T. Oravecz, et al. (2012)
Blood 120, 3764-3773
   Abstract »    Full Text »    PDF »
The puzzling origin of lymphocytes.
C. Muller-Sieburg (2012)
Blood 119, 5609-5610
   Full Text »    PDF »
Lin-28 Homologue A (LIN28A) Promotes Cell Cycle Progression via Regulation of Cyclin-dependent Kinase 2 (CDK2), Cyclin D1 (CCND1), and Cell Division Cycle 25 Homolog A (CDC25A) Expression in Cancer.
N. Li, X. Zhong, X. Lin, J. Guo, L. Zou, J. L. Tanyi, Z. Shao, S. Liang, L.-P. Wang, W.-T. Hwang, et al. (2012)
J. Biol. Chem. 287, 17386-17397
   Abstract »    Full Text »    PDF »
Distinct B-cell lineage commitment distinguishes adult bone marrow hematopoietic stem cells.
E. E. B. Ghosn, R. Yamamoto, S. Hamanaka, Y. Yang, L. A. Herzenberg, H. Nakauchi, and L. A. Herzenberg (2012)
PNAS 109, 5394-5398
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882