期刊
BLOOD
卷 99, 期 7, 页码 2369-2378出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood.V99.7.2369
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- NHLBI NIH HHS [HL 45851] Funding Source: Medline
- NIDDK NIH HHS [DK 02761, DK 50234] Funding Source: Medline
Hematopoietic stem cells sequentially pass through a series of decision points affecting self-renewal or lineage-specific differentiation. Notch1 receptor is a known modulator of lineage-specific events in hematopoiesis that we assessed in the context of in vivo stem cell kinetics. Using RAG-1(-/-) mouse stems cells, we documented increased stem cell numbers due to decreased differentiation and enhanced stem cell self-renewal induced by Notch1. Unexpectedly, preferential lymphoid, over myeloid lineage commitment was noted when differentiation occurred. Therefore, Notch1 iaffects 2 decision points in stem cell regulation, favoring self-renewal over differentiation and lymphoid over myeloid lineage outcome. Notch1 offers an attractive target for stem cell manipulation strategies, particularly in the context of immunodeficiency and acquired immunodeficiency syndrome.
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