title: Notch1 activation increases hematopoietic stem cell self-renewal in vivo and favors lymphoid over myeloid lineage outcome.
abstract: 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 affects 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.
authors.affiliation: Partners AIDS Research Center, MGH Cancer Center, Massachusetts General Hospital, 149 13th Street, Boston, MA 02129, USA.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Stier
authors.forename: Tao
authors.initials: T
authors.lastname: Cheng
authors.forename: David
authors.initials: D
authors.lastname: Dombkowski
authors.forename: Nadia
authors.initials: N
authors.lastname: Carlesso
authors.forename: David T
authors.initials: DT
authors.lastname: Scadden
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000502:physiology; D002455:Cell Division; D002460:Cell Line; D003114:Colony-Forming Units Assay; D005786:Gene Expression Regulation / Q000502:physiology; D016654:Genes, RAG-1; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007668:Kidney; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D009024:Morphogenesis; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D014157:Transcription Factors; D014162:Transfection
chemical_list: D018398:Homeodomain Proteins; D008565:Membrane Proteins; C497761:NOTCH1 protein, human; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D014157:Transcription Factors; C064658:RAG-1 protein