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
Dept. of Immunology, Institute of Basic Medical Sciences, University of Tsukuba and CREST (JST), 1-1-1 Tennodai, Tsukuba 305-8575, Japan.81-298-53-696681-298-53-6964

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 ofthe mouse were first evaluated in serum-free single cell culture.We then performed a competitive repopulation assay on dividedcells to ask if such cell division involved self-renewal ofHSCs.

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

Abbreviations used in this paper: HSCs, hematopoietic stem cells;SCF, stem cell factor; TPO, thrombopoietin.

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