Murine hematopoietic stem cells and multipotent progenitors express truncated intracellular form of c-kit receptor.

Jennifer Zayas, Danislav S. Spassov, Ronald G. Nachtman, Roland Jurecic

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The c-kit receptor plays a vital role in self-renewal and differentiation of hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs). We have discovered that besides c-kit, the murine multipotent HSC/MPP-like cell line EML expresses the transcript and protein for a truncated intracellular form of c-kit receptor, called tr-kit. Notably, the tr-kit transcript and protein levels were down-regulated during cytokine-induced differentiation of the HSC/MPP-like cell line EML into myeloerythroid lineages. These findings prompted us to analyze tr-kit expression in purified murine fetal liver and bone marrow cell populations containing long-term repopulating (LTR) HSCs, short-term repopulating (STR) HSCs, MPPs, lineage-committed progenitors, and immature blood cells. Remarkably, these studies have revealed that in contrast to more widespread expression of c-kit, tr-kit is transcribed solely in cell populations enriched for LTR-HSCs, STR-HSCs, and MPPs. On the other hand, cell populations in which HSCs and MPPs are either present at a much lower frequency or are absent altogether, cells representing more advanced stages of differentiation into lymphoid and myeloid lineages do not express tr-kit. The observation that tr-kit is co-expressed with c-kit only in more primitive HSC- and MPP-enriched cell populations raises an exciting possibility that tr-kit functions either as a new component of the stem cell factor (SCF)/c-kit pathway or is involved in a novel signaling pathway, present exclusively in HSC and MPPs. Taken together, these findings necessitate functional characterization of tr-kit and analysis of its potential role in the self-renewal, proliferation, and/or differentiation of HSC and multipotent progenitors.

Original languageEnglish
Pages (from-to)343-353
Number of pages11
JournalStem Cells and Development
Volume17
Issue number2
DOIs
StatePublished - Apr 1 2008

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Proto-Oncogene Proteins c-kit
Hematopoietic Stem Cells
Stem Cells
Population
Multipotent Stem Cells
Cell Line
Stem Cell Factor
Bone Marrow Cells
Blood Cells
Proteins

ASJC Scopus subject areas

  • Hematology

Cite this

Murine hematopoietic stem cells and multipotent progenitors express truncated intracellular form of c-kit receptor. / Zayas, Jennifer; Spassov, Danislav S.; Nachtman, Ronald G.; Jurecic, Roland.

In: Stem Cells and Development, Vol. 17, No. 2, 01.04.2008, p. 343-353.

Research output: Contribution to journalArticle

Zayas, Jennifer ; Spassov, Danislav S. ; Nachtman, Ronald G. ; Jurecic, Roland. / Murine hematopoietic stem cells and multipotent progenitors express truncated intracellular form of c-kit receptor. In: Stem Cells and Development. 2008 ; Vol. 17, No. 2. pp. 343-353.
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