Download Manipulation of the hematopoietic stem cell (HSC) niche for the ex vivo expansion of HSCs

NUS Graduate School for Integrative Sciences and Engineering
Research Project Write-up
Title of Project 1 :
Name of
Supervisor:
Contact Details:
Manipulation of the hematopoietic stem cell (HSC)
niche for the ex vivo expansion of HSCs
Toshio Suda
+65 6516 1166
Email : [email protected]
Short Description
Hematopoietic stem cells (HSCs) in the BM are regulated in a specialized
microenvironment, the stem cell niche. Signals from the niche along with cell
autonomous regulations are necessary for the self-renewal and proliferation of
HSCs. In this project we aim to characterize cell components in the niche and
identify novel factors produced by niche cells involved in the maintenance of HSCs.
Identification of such factors will provide essential keys for the manipulation and
expansion of HSCs, ex vivo, and allow usage of HSCs in clinical therapies for
blood-related diseases.
Title of Project 2 :
Elucidation of niche involvement in the pathophysiology of
hematopoietic malignancies along with the identification
of molecular targets of diseases.
Short Description
Resembling solid tumor cells, leukemic stem cells (LSCs) are situated in a hypoxic
environment. We found recently that leukemic cells specifically upregulates
hypoxic inducible factors (HIFs) and other genes that regulate cell-cell interaction.
These targets might represent a novel mechanism in how tissue metabolic status
connecting to cellular interaction.
Title of Project 3 :
Identification of stemness-related cis-regulatory
elements
Short Description
Gene expression is regulated by promoters and distal cis-regulatory elements.
Enhancers are more cell type specific in comparison to promoters, and it is known
that even genes expressed broadly can show a vast difference in enhancer usage
across distinct differentiation stages. However, the nature of enhancer usage in
HSC is unclear. To dissect the cellular and molecular character of HSCs, we are
seeking stemness-related cis-regulatory elements, combining in silico screening
and further validation of in vivo functionality using zebrafish and mice.
Title of Project 4:
Establishment of human stem cell niche in
immunodeficient mouse
Short Description
Patient-derived leukemic xenograft model is important tool for basic as well as
translational research. Successful xenograft remains difficult, possibly due to the
lack of human niche components for leukemic cells. By implanting human niche
cells, we are establishing in vivo, humanized bone marrow model in
immunodeficient mice.