2007 Fiscal Year Final Research Report Summary
Molecular mechanism of leukemica stem cells maintenance in vivo
| Project/Area Number |
18390285
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Tokai University |
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Principal Investigator |
ANDO Kiyoshi Tokai University, School of Medicine, department of Medicine, MD, PhD Professor (70176014)
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| Co-Investigator(Kenkyū-buntansha) |
YAHATA Takashi Tokai University, School of Medicine, department of Medicine, Assistant Professor (10398753)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Hematopoietic stem cells / Immunedeficient mice / BM niche / Myelodysplastic syndrome / CD34 / Intra-BM transplantation |
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| Research Abstract |
Human hematopoietic stem (HSC) cell compartment is heterogeneous. To understand how the long-term repopulating cell (LTRC) activity of individual HSCs and the hematopoietic hierarchy are maintained in the bone marrow microenvironment, we traced the repopulating dynamics of individual HSC clones by virus integration site analysis. Our clonal analysis, coupled with histological examination, revealed that quiescent CD34+CD38neg cells in the niche were human LTRCs responsible for creating hematopoietic hierarchy and that quiescent LTRCs localizing to the niche produced both LTRCs and short-term repopulating cells (STRCs) by asymmetrical self-renewal division. We further demonstrated that human mesenchymal stem cells differentiated into the key components of niche and functioned in maintaining LTRC activity both by closely interacting with quiescent human LTRCs and secreting hematopoietic-regulatory factors. Our study successfully demonstrated how individual functional elements of the hematopoiesis orchestrated to create human hematopoietic hierarchy in the hematopoietic microenvironment. Furthermore, we transplanted cells derived from myelodysplastic syndrome into mice and confirmed engraftment of them.
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