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PMID: 9755174 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Expression of the LIM-homeobox gene LH2 generates immortalized steel factor-dependent multipotent hematopoietic precursors.

The EMBO journal ·Vol. 17 ·No. 19 ·1998-10-01 ·Pages 5744-56

Pinto do O P, Kolterud A, Carlsson L

Abstract

The genes controlling self-renewal and differentiation in the hematopoietic system are largely unknown. The LIM-homeobox genes are known to be important for asymmetric cell divisions and differentiation of specific cell types and organs. One member of this family, LH2, is expressed in fetal liver at the time of active hematopoiesis. Therefore, we have assessed the function of LH2 during the formation and initial expansion of the hematopoietic system by differentiating LH2-transduced embryonic stem (ES) cells in vitro. This procedure generated multipotent hematopoietic precursor cell (HPC) lines that required Steel factor for growth. HPC lines have been maintained in an undifferentiated state in culture for >7 months. Other growth factors tested efficiently induce terminal differentiation of HPCs into various mature myeloid lineages. Steel factor is also required and acts synergistically with the other growth factors to generate multilineage colonies from the HPCs. These HPC lines express transcription factors that are consistent with an immature progenitor, and the pattern of cell surface marker expression is similar to that of early fetal multipotent hematopoietic progenitors. Collectively, these data suggest that the HPC lines represent an early fetal multipotent hematopoietic progenitor, and suggest a role for LH2 in the control of cell fate decision and/or proliferation in the hematopoietic system.

MeSH Terms
Animals Antigens, Differentiation Cell Differentiation Cell Line, Transformed Cell Lineage Down-Regulation Genes, Homeobox Genetic Vectors Hematopoiesis/genetics Hematopoietic Stem Cells/cytology,drug effects Homeodomain Proteins/biosynthesis,genetics LIM-Homeodomain Proteins Mice RNA, Messenger/analysis Recombinant Proteins/biosynthesis Retroviridae/genetics Stem Cell Factor/pharmacology Transcription Factors/analysis,biosynthesis,genetics Transformation, Genetic
Chemicals
Antigens, Differentiation Homeodomain Proteins LIM-Homeodomain Proteins LIM-homeodomain protein LH-2 Lhx2 protein, mouse RNA, Messenger Recombinant Proteins Stem Cell Factor Transcription Factors
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Pinto do O P
Department of Microbiology, University of Umeå, 901 87 Umeå, Sweden.
Kolterud A
Carlsson L
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/17.19.5744
Published
1998-10-01
Pages
5744-56
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1170902
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/17.19.5744 PMC Full Text View journal details
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