ABSTRACT Hematopoietic stem cells give rise to progeny that either self-renew in an undifferentiated state or lose self-renewal capabilities and commit to lymphoid or myeloid lineages. Here

we evaluated whether hematopoietic stem cell self-renewal is affected by the Notch pathway. Notch signaling controls cell fate choices in both invertebrates and vertebrates1,2,3,4,5,6,7 by

inhibiting certain differentiation pathways, thereby permitting cells to either differentiate along an alternative pathway or to self-renew1. Notch receptors are present in hematopoietic

precursors and Notch signaling enhances the _in vitro_ generation of human and mouse hematopoietic precursors8,9,10,11,12,13,14,15, determines T- or B-cell lineage specification from a

regulating hematopoietic stem cell self-renewal. Furthermore, the establishment of clonal, pluripotent cell lines provides the opportunity to assess mechanisms regulating stem cell

commitment and demonstrates a general method for immortalizing stem cell populations for further analysis. Access through your institution Buy or subscribe This is a preview of subscription

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HEMATOPOIETIC STEM CELL EMERGENCE VIA NOTCH SIGNALING IN VERTEBRATES Article Open access 03 January 2024 THE UNIVERSAL STEM CELL Article Open access 28 October 2022 SYSTEMATIC IDENTIFICATION

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homozygous for a processing deficient Notch1 allele. _Nature_ 405, 966– 970 (2000). Article  CAS  Google Scholar  Download references ACKNOWLEDGEMENTS We thank M. Linenberger, S. Collins

and K. Ohishi for criticism of the manuscript. This work was supported by grants P50 HL54881, RO1-CA82308-01 and RO1-AI47833-01 from the National Institutes of Health. I.D.B is also

supported as an American Cancer Society-F.M. KirbyClinical Research Professorship, and W.S.P is the recipient of a Scholar Award from the Leukemia and Lymphoma Society. AUTHOR INFORMATION

AUTHORS AND AFFILIATIONS * Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., D2-373, Seattle, 98109, Washington, USA Barbara Varnum-Finney, Carolyn

Brashem-Stein, Cynthia Nourigat, David Flowers & Irwin D. Bernstein * Department of Pathology and Institute for Medicine and Engineering, 611 BRB II/III, 421 Curie Blvd. Lanwei Xu, Sonia

Bakkour & Warren S. Pear * University of Pennsylvania, Philadelphia, 19104, Pennsylvania, USA Lanwei Xu, Sonia Bakkour & Warren S. Pear * The Department of Pediatrics, The

University of Washington, Seattle, 98105, Washington, USA Irwin D. Bernstein Authors * Barbara Varnum-Finney View author publications You can also search for this author inPubMed Google

Scholar * Lanwei Xu View author publications You can also search for this author inPubMed Google Scholar * Carolyn Brashem-Stein View author publications You can also search for this author

inPubMed Google Scholar * Cynthia Nourigat View author publications You can also search for this author inPubMed Google Scholar * David Flowers View author publications You can also search

for this author inPubMed Google Scholar * Sonia Bakkour View author publications You can also search for this author inPubMed Google Scholar * Warren S. Pear View author publications You can

also search for this author inPubMed Google Scholar * Irwin D. Bernstein View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR

Correspondence to Barbara Varnum-Finney. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Varnum-Finney, B., Xu, L., Brashem-Stein, C. _et al._

Pluripotent, cytokine-dependent, hematopoietic stem cells are immortalized by constitutive Notch1 signaling. _Nat Med_ 6, 1278–1281 (2000). https://doi.org/10.1038/81390 Download citation *

Received: 15 June 2000 * Accepted: 27 September 2000 * Issue Date: November 2000 * DOI: https://doi.org/10.1038/81390 SHARE THIS ARTICLE Anyone you share the following link with will be able

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