- Hematopoietic Stem Cell Transplantation
- T-cell and B-cell Immunology
- Acute Myeloid Leukemia Research
- Mesenchymal stem cell research
- Immune Cell Function and Interaction
- Zebrafish Biomedical Research Applications
- Neonatal Respiratory Health Research
- Immune cells in cancer
- Pluripotent Stem Cells Research
- Cancer Cells and Metastasis
- Immunotherapy and Immune Responses
- Epigenetics and DNA Methylation
- Platelet Disorders and Treatments
- Cytokine Signaling Pathways and Interactions
- Hematological disorders and diagnostics
- Single-cell and spatial transcriptomics
- Acute Lymphoblastic Leukemia research
- RNA Interference and Gene Delivery
- Cancer Genomics and Diagnostics
- Renal and related cancers
- CRISPR and Genetic Engineering
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- T-cell and Retrovirus Studies
- Liver physiology and pathology
- Virus-based gene therapy research
Institute of Hematology & Blood Diseases Hospital
2015-2025
Chinese Academy of Medical Sciences & Peking Union Medical College
2015-2025
Keio University
2008-2021
Peking Union Medical College Hospital
2016-2019
UNSW Sydney
2019
Academy of Medical Sciences
2017
State Key Laboratory of Chemical Engineering
2016
The University of Tokyo
2003-2013
Tokyo University of Science
2003-2013
Regenerative Medicine Institute
2009
Little is known of age-associated functional changes in hematopoietic stem cells (HSCs). We studied aging HSCs at the clonal level by isolating CD34−/lowc-Kit+Sca-1+ lineage marker–negative (CD34−KSL) from bone marrow C57BL/6 mice. A population CD34−KSL gradually expanded as age increased. Regardless age, these formed vitro colonies with cell factor and interleukin (IL)-3 but not IL-3 alone. They did form day 12 colony-forming unit (CFU)-S, indicating that they are primitive myeloid...
Hematopoietic stem cells (HSCs) have been extensively characterized based on functional definitions determined by experimental transplantation into lethally irradiated mice. In mice, HSCs are heterogeneous with regard to self-renewal potential, in vitro colony-forming activity, and vivo behavior. We attempted prospective isolation of HSC subsets distinct properties among CD34−/low c-Kit+Sca-1+Lin− (CD34−KSL) cells. CD34−KSL were divided, CD150 expression, three fractions: CD150high,...
Little is known about how hematopoietic stem cells (HSCs) self-renew. We studied the regeneration of HSCs in culture. Effects various cytokines on cell division CD34−/low c-Kit+Sca-1+ lineage marker–negative (CD34−KSL) bone marrow mouse were first evaluated serum-free single then performed a competitive repopulation assay divided to ask if such involved self-renewal HSCs. In presence factor (SCF), thrombopoietin (TPO) induced CD34−KSL more efficiently than did interleukin (IL)-3 or IL-6....
How hematopoietic stem cells (HSCs) commit to a particular lineage is unclear. A high degree of HSC purification enabled us address this issue at the clonal level. Single-cell transplantation studies revealed that 40% CD34−/low, c-Kit+, Sca-1+, and marker− (CD34−KSL) in adult mouse bone marrow were able, as individual cells, reconstitute myeloid B- T-lymphoid lineages over long-term. culture showed >40% CD34−KSL could form neutrophil (n)/macrophage (m)/erythroblast (E)/megakaryocyte...
DNA methylation is an epigenetic modification essential for development. The methyltransferases Dnmt3a and Dnmt3b execute de novo in gastrulating embryos differentiating germline cells. It has been assumed that these enzymes generally play a role regulating cell differentiation. To test this hypothesis, we examined the of adult stem CD34−/low, c-Kit+, Sca-1+, lineage marker− (CD34− KSL) cells, fraction mouse bone marrow cells highly enriched hematopoietic (HSCs), expressed both Dnmt3b. Using...
One of the central tasks stem cell biology is to understand molecular mechanisms that control self-renewal in cells. Several cytokines are implicated as crucial regulators hematopoietic cells (HSCs), but little known about intracellular signaling for HSC self-renewal. To address this issue, we attempted clarify how potential enhanced HSCs without adaptor molecule Lnk, Lnk-deficient mice expanded number >10-fold because their increased potential. We show Lnk negatively regulates by modifying...
Angiogenesis and lymphangiogenesis are complex phenomena that involve the interplay of several growth factors receptors. Recently, we have demonstrated in Keratin-14 (K14) promoter-driven Vegf-A transgenic (Tg) mice, not only angiogenesis but also is stimulated. However, mechanism by which VEGFR1 involved remains unclear.To examine how important tyrosine kinase (TK) K14 Tg crossed mice with VEGFR1-TK-deficient to generate double mutant Vegfr1 tk(-/-) mice. exhibit a remarkable decrease...
Emergency myelopoiesis is inflammation-induced hematopoiesis to replenish myeloid cells in the periphery, which critical control infection with pathogens. Previously, pro-inflammatory cytokines such as interferon (IFN)-α and IFN-γ were demonstrated play a role expansion of hematopoietic stem (HSCs) progenitors, leading production mature cells, although their inhibitory effects on also reported. Therefore, molecular mechanism emergency during remains incompletely understood. Here, we clarify...
Transforming growth factor β1 (TGF-β1) plays a role in the maintenance of quiescent hematopoietic stem cells (HSCs) vivo. We asked whether TGF-β1 controls cell cycle status HSCs vitro to enhance reconstitution activity. To examine effect on HSC function, we used an culture system which single divide with retention their short- and long-term ability. Extensive single-cell analyses showed that, regardless its concentration, slowed down progression but consequently suppressed self-renewal...
To detect as yet unidentified cell-surface molecules specific to hematopoietic stem cells (HSCs), a modified signal sequence trap was successfully applied mouse bone marrow (BM) CD34−c-Kit+Sca-1+Lin− (CD34−KSL) HSCs. One of the identified molecules, Endomucin, is an endothelial sialomucin closely related CD34. High-level expression Endomucin confined BM KSL HSCs and progenitor cells, and, importantly, long-term repopulating (LTR)–HSCs were exclusively present in Endomucin+CD34−KSL...