Human CD34(lo)CD133(lo) fetal liver cells support the expansion of human CD34(hi)CD133(hi) hematopoietic stem cells.
We have recently discovered a unique CD34(lo)CD133(lo) cell population in the human fetal liver (FL) that gives rise to cells in the hepatic lineage. In this study, we further characterized the biological functions of FL CD34(lo)CD133(lo) cells. Our findings show that these CD34(lo)CD133(lo) cells express markers of both endodermal and mesodermal lineages and have the capability to differentiate into hepatocyte and mesenchymal lineage cells by ex vivo differentiation assays. Furthermore, we show that CD34(lo)CD133(lo) cells express growth factors that are important for human hematopoietic stem cell (HSC) expansion: stem cell factor (SCF), insulin-like growth factor 2 (IGF2), C-X-C motif chemokine 12 (CXCL12), and factors in the angiopoietin-like protein family. Co-culture of autologous FL HSCs and allogenic HSCs derived from cord blood with CD34(lo)CD133(lo) cells supports and expands both types of HSCs.These findings are not only essential for extending our understanding of the HSC niche during the development of embryonic and fetal hematopoiesis but will also potentially benefit adult stem cell transplantations in clinics because expanded HSCs demonstrate the same capacity as primary cells to reconstitute the human immune system and mediate long-term hematopoiesis in vivo. Together, CD34(lo)CD133(lo) cells not only serve as stem/progenitor cells for liver development but are also an essential component of the HSC niche in the human FL.
Humanized Mouse Unit, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore 138673, Singapore.
Kylie Su Mei
KS
Yong
Humanized Mouse Unit, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore 138673, Singapore.
Choong Tat
CT
Keng
Department of Obstetrics & Gynaecology, KK Women's and Children's Hospital, Singapore 229899, Singapore.
Shu Qi
SQ
Tan
Department of Pathology and Laboratory Medicine, KK Women's and Children's Hospital, Singapore 229899, Singapore.
Eva
E
Loh
Department of Pathology and Laboratory Medicine, KK Women's and Children's Hospital, Singapore 229899, Singapore.|Duke-NUS Graduate Medical School, Singapore 169857, Singapore.
Kenneth Te
KT
Chang
Department of Obstetrics & Gynaecology, KK Women's and Children's Hospital, Singapore 229899, Singapore.|Duke-NUS Graduate Medical School, Singapore 169857, Singapore.
Thiam Chye
TC
Tan
Humanized Mouse Unit, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore 138673, Singapore.
Wanjin
W
Hong
Humanized Mouse Unit, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore 138673, Singapore.|Interdisciplinary Research Group in Infectious Diseases, Singapore-Massachusetts Institute of Technology Alliance for Research and Technology, Singapore 138602, Singapore.|Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore.
Qingfeng
Q
Chen
D000071916:AC133 Antigen / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D018952:Antigens, CD34 / Q000378:metabolism*; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D018920:Coculture Techniques; D005260:Female; D005333:Fetus / Q000166:cytology*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008099:Liver / Q000166:cytology* / Q000196:embryology*; D008297:Male; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D010641:Phenotype
D000071916:AC133 Antigen; D018952:Antigens, CD34; D036341:Intercellular Signaling Peptides and Proteins