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PMID: 16357205 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Embryonic stem cell-derived hematopoietic stem cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 102 ·No. 52 ·2005-12-27 ·Pages 19081-6

Wang Y, Yates F, Naveiras O, Ernst P, Daley GQ

Abstract

Despite two decades of studies documenting the in vitro blood-forming potential of murine embryonic stem cells (ESCs), achieving stable long-term blood engraftment of ESC-derived hematopoietic stem cells in irradiated mice has proven difficult. We have exploited the Cdx-Hox pathway, a genetic program important for blood development, to enhance the differentiation of ESCs along the hematopoietic lineage. Using an embryonic stem cell line engineered with tetracycline-inducible Cdx4, we demonstrate that ectopic Cdx4 expression promotes hematopoietic mesoderm specification, increases hematopoietic progenitor formation, and, together with HoxB4, enhances multilineage hematopoietic engraftment of lethally irradiated adult mice. Clonal analysis of retroviral integration sites confirms a common stem cell origin of lymphoid and myeloid populations in engrafted primary and secondary mice. These data document the cardinal stem cell features of self-renewal and multilineage differentiation of ESC-derived hematopoietic stem cells.

MeSH Terms
Animals Antigens, Surface/chemistry Blotting, Southern Cell Differentiation Cell Line Cell Lineage Cell Separation Cell Transplantation DNA/chemistry Embryo, Mammalian/cytology Flow Cytometry Gene Expression Regulation Hematopoiesis/physiology Hematopoietic Stem Cells/cytology Homeodomain Proteins/metabolism Humans Male Mesoderm/metabolism Mice Reverse Transcriptase Polymerase Chain Reaction Spleen/cytology Stem Cells/cytology Time Factors Transgenes
Chemicals
Antigens, Surface Cdx4 protein, mouse Homeodomain Proteins DNA
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Wang Yuan
Division of Hematology/Oncology, Children's Hospital Boston, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Division of Hematology, Brigham and Women's Hospital, Harvard Stem Cell Institute, Boston, MA 02115, USA.
Yates Frank
Naveiras Olaia
Ernst Patricia
Daley George Q
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0506127102
Published
2005-12-27
Epub
2005-00-15
Pages
19081-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC1323159
Subset
IM
Corrections
ErratumIn
PMID: 34312242
External Links
PubMed source DOI: 10.1073/pnas.0506127102 PMC Full Text View journal details
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