Cell Cycle Quiescence of Early Lymphoid Progenitors in Adult Bone Marrow
Open Access
- 1 December 2006
- journal article
- research article
- Published by Oxford University Press (OUP) in The International Journal of Cell Cloning
- Vol. 24 (12), 2703-2713
- https://doi.org/10.1634/stemcells.2006-0217
Abstract
Lymphocyte production in bone marrow (BM) requires substantial cell division, but the relationship between largely quiescent stem cells and dividing lymphoid progenitors is poorly understood. Therefore, the proliferation and cell cycle status of murine hematopoietic progenitors that have just initiated the lymphoid differentiation program represented the focus of this study. Continuous bromo‐2′‐deoxyuridine (BrdU) incorporation and DNA/RNA analysis by flow cytometry revealed that a surprisingly large fraction of RAG‐1+c‐kithi early lymphoid progenitors (ELPs) and RAG‐1+c‐kitlo pro‐lymphocytes (Pro‐Ls) in adult BM were in cell cycle quiescence. In contrast, their counterparts in 14‐day fetal liver actively proliferated. Indeed, the growth fraction (cells in G1‐S‐G2‐M phases) of fetal ELPs was on average 80% versus only 30% for adult ELPs. After 5‐fluorouracil treatment, as many as 60% of the adult ELP‐enriched population was in G1‐S‐G2‐M and 34% incorporated BrdU in 6 hours. Transcripts for Bcl‐2, p21Cip1/Waf1, and p27 Kip1 cell cycle regulatory genes correlated inversely well with proliferative activity. Interestingly, adult lymphoid progenitors in rebound had the high potential for B lymphopoiesis in culture typical of their fetal counterparts. Thus, lymphocyte production is sustained during adult life by quiescent primitive progenitors that divide intermittently. Some, but not all, aspects of the fetal differentiation program are reacquired after chemotherapy.Keywords
This publication has 68 references indexed in Scilit:
- Tracing the first waves of lymphopoiesis in miceDevelopment, 2006
- Life before the pre-B cell receptor checkpoint: Specification and commitment of primitive lymphoid progenitors in adult bone marrowSeminars in Immunology, 2006
- Ubiquitylation of RAG-2 by Skp2-SCF Links Destruction of the V(D)J Recombinase to the Cell CycleMolecular Cell, 2005
- Identification of Flt3+ Lympho-Myeloid Stem Cells Lacking Erythro-Megakaryocytic PotentialCell, 2005
- Recombination-activating gene proteins: more regulation, pleaseImmunological Reviews, 2004
- Unique Properties of Fetal Lymphoid Progenitors Identified According to RAG1 Gene ExpressionImmunity, 2003
- Localization of recombination activating gene 1/green fluorescent protein (RAG1/GFP) expression in secondary lymphoid organs after immunization with T-dependent antigens in rag1/gfpknockin miceBlood, 2001
- Apoptosis and its modulation during B lymphopoiesis in mouse bone marrowImmunological Reviews, 2000
- Changes in Markers, Receptors and Adhesion Molecules Expressed on Murine Hemopoietic Stem Cells After a Single Injection of 5‐FluorouracilThe International Journal of Cell Cloning, 1996
- Two Pathways of B‐Lymphocyte Development in Mouse Bone Marrow and the Roles of Surrogate L Chain in this DevelopmentImmunological Reviews, 1994