In Vitro Self-Renewal Division of Hematopoietic Stem Cells

doi:10.1084/jem.192.9.1281

Published online 6 November 2000.

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© The Rockefeller University Press, 0022-1007/2000/11/1281/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 9, November 6, 2000 1281-1288

Original Article

In Vitro Self-Renewal Division of Hematopoietic Stem Cells

Hideo Ema^a, Hina Takano^a, Kazuhiro Sudo^a, and Hiromitsu Nakauchi^a
^a Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba and Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Tsukuba 305-8575, Japan

Correspondence to: Hiromitsu Nakauchi, Dept. of Immunology, Institute of Basic Medical Sciences, University of Tsukuba and CREST (JST), 1-1-1 Tennodai, Tsukuba 305-8575, Japan. Tel:81-298-53-6964 Fax:81-298-53-6966

Little is known about how hematopoietic stem cells (HSCs) self-renew.We studied the regeneration of HSCs in culture. Effects of variouscytokines on cell division of CD34^-/low c-Kit⁺Sca-1⁺ lineagemarker–negative (CD34^-KSL) bone marrow cells of the mousewere first evaluated in serum-free single cell culture. We thenperformed a competitive repopulation assay on divided cellsto ask if such cell division involved self-renewal of HSCs.

In the presence of stem cell factor (SCF), thrombopoietin (TPO)induced a first cell division of CD34^-KSL cells more efficientlythan did interleukin (IL)-3 or IL-6. Multilineage repopulatingcells were detected in a significant proportion of cells derivedfrom single cells in culture with TPO and SCF, although thisculture condition led to a substantial decrease in HSC number.These regenerated repopulating cells could be further transplantedinto secondary recipients. When paired daughter cells were separatelystudied, one of a pair gave rise to repopulating cells withself-renewal potential, suggesting asymmetric self-renewal division.This study provides evidence that one HSC regenerates at leastone HSC in culture.

Key Words: mouse, bone marrow transplantation, hematopoiesis, self-renewal,cell division

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