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Tissue-Specific Stem Cells
Article first published online: 22 MAY 2013
Copyright © 2013 AlphaMed Press
Volume 31, Issue 6, pages 1160–1169, June 2013
How to Cite
Chen, Q., Khoury, M., Limmon, G., Choolani, M., Chan, J. K.Y. and Chen, J. (2013), Human Fetal Hepatic Progenitor Cells Are Distinct from, but Closely Related to, Hematopoietic Stem/Progenitor Cells. STEM CELLS, 31: 1160–1169. doi: 10.1002/stem.1359
Author contributions: Q.C.: conception and design, collection and assembly of data, data analysis and interpretation, and manuscript preparation; M.K.: data analysis and interpretation and manuscript preparation; G.L.: data analysis and interpretation; M.C.: provision of study materials and clinical samples; J.KY.C.: provision of study materials and clinical samples and manuscript preparation; J.C.: conception and design, data analysis and interpretation, and manuscript preparation.
Disclosure of potential conflicts of interest is found at the end of this article.
first published online in STEM CELLS EXPRESS February 13, 2013.
- Issue published online: 22 MAY 2013
- Article first published online: 22 MAY 2013
- Accepted manuscript online: 13 FEB 2013 06:19AM EST
- Manuscript Accepted: 20 JAN 2013
- Manuscript Received: 26 SEP 2012
- National Medical Research Council, Singapore. Grant Numbers: CSA/009/2009, CSA/012/2009
- National Research Foundation Singapore
- Singapore-MIT Alliance for Research and Technology's Infectious Disease IRG research program
Additional Supporting Information may be found in the online version of this article.
|sc-12-0900_sm_SupplFigure1.tif||3435K||Fig. S1. (A) CD34loCD133lo cells from human fetal liver are larger in size than CD34hiCD133hi and CD34hiCD133neg cells. CD34+ cells were isolated from single cell suspensions of fetal liver by magnetic cell sorting and stained for CD34 and CD133. Representative staining profiles of CD34 versus CD133 are shown (top) for CD34+ cells, and FSC versus SSC profile (middle panel) for the gated CD34loCD133lo, CD34hiCD133neg, and CD34hiCD133hi subpopulations. After purification, the three subpopulations were stained by Giemsa (bottom panel). Scale bar applies to all panels. Shown are representative data from 3 different fetal liver samples. (B) Identification of human cells in the mouse liver by fluorescence in situ hybridization. Liver sections were stained with a Cy3-conjugated (red) anti-human pan centromere probe and DAPI (blue). Sections of human fetal liver were used as a positive control and liver sections from a non-reconstituted NSG mice were used as a negative control. The boxed areas are shown at higher magnifications at the bottom row. White arrows point to human centromere-positive cells in a liver section of a mouse that had been engrafted with CD34loCD133lo human fetal liver cells. Scale bars are shown. Shown are representative data from 5 humanized mice, 2 NSG mice and 1 human fetal liver sample.|
|sc-12-0900_sm_SupplFigure2.tif||1596K||Fig. S2. Change in cell morphology and cell number of cultured CD34loCD133lo cells over time. Representative phase-contrast micrographs from one of the three different cultures are shown for cells at 2, 14 and 28 days (A). Scale bars are indicated. Cells in the culture were trypsinized and counted every 7 days, and the total cell number (B) at a given day was calculated by multiplying the cell number from manual counting by dilutions based on numbers of passages. Data shown are average ± SEM from three different fetal liver samples, each with duplicate culture wells.|
|sc-12-0900_sm_SupplFigure3.tif||1654K||Fig. S3. Differentiation of human fetal liver CD34hiCD133hi cells in NSG recipient mice. Purified CD34hiCD133hi cells (1×105 per recipient) were injected intra-cardially into newborn NSG mice. Ten weeks post injection, splenocytes were stained for human CD45, CD3, CD19, CD56, CD14, CD11c, BDCA-1, CD303, or ILT7, and mouse CD45. Representative staining profiles are shown for CD3 versus CD19, CD14 versus CD56, CD11c versus BDCA-1, and CD303 versus ILT7, gating on hCD45+ cells from one of ten mice reconstituted with cells from two different fetal liver samples. The numbers indicate percentages of cells in the gated regions.|
|sc-12-0900_sm_SupplFigure4.tif||1206K||Fig. S4. Comparison of surface phenotype of selected markers between fetal HPCs and HSPCs from fetal liver (FL HSPC) and cord blood (CB HSPC). Staining profiles of CD44, CD117, EpCAM, CD90, CD105, CD97, CD24, CD73, CD166 and CD45 are shown as histograms for CD34loCD133lo HPCs and CD34hiCD133hi HSPCs from fetal liver and cord blood. Dark line: stained with specific antibodies; thin line: isotype controls.|
|sc-12-0900_sm_SupplFigure5.tif||812K||Fig. S5. (A) Principal component analysis (PCA) of the microarray data; a three dimensional plot of PCA is depicted. Each data point represents an individual sample/array, and all 12 sample/arrays are presented on the plot. The percentage values indicate the proportion of total variance, as described by each PC. PC 1, principal component 1 (×-axis); PC 2, principal component 2 (Y-axis); PC 3, principal component 3 (Z-axis). Arrays are distinguished by color; replicates are represented by different symbols of the same color. FL HPC, CD34hiCD133neg, FL HSPC and CB HSPC samples/arrays aggregate together, pointing to the similarity in their expression profiles. However, the profile of hepatocytes is distinct from that of the others. (B) Comparison of gene expression among HPCs, FL HSPCs, CB HSPCs, and hepatocytes. The number of genes that are upregulated 5-fold in both HPCs and FL HSPCs are shown in relation to those in hepatocytes or in CB HSPCs. *p<0.001.|
|sc-12-0900_sm_SupplTable1.pdf||41K||Supplementary Table 1.|
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