Phenotypic and functional characterization of committed and primitive myeloid and lymphoid hematopoietic precursors in human fetal liver

Vivek Roy, J. S. Miller, C. M. Verfaille

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

We studied the phenotypic and functional properties of colony-forming cells (CFCs), primitive long-term culture initiating cells (LTC-ICs) and lymphoid precursors present in human fetal liver (FL) and compared these with their adult bone marrow (BM) counterparts. FL (7-14-week) cells were selected by fluorescence-activated cell sorting based on increasing CD34 antigen expression (34+, 34++, or 34+++), CD38 antigen expression (CD34(++/+++)CD38+, or CD38-), and HLA-DR antigen expression (CD34(++/+++)HLA-DR+ or HLA-DR-). 13 ± 0.6% of FL CD34-positive cells were 34+++. Significantly more FL CD34(++/+++) cells were CD38- (49 ± 2.4%) and HLA-DR- (72 ± 6.7%) than BM CD34++ cells (6.8 ± 0.7% CD38- and 13.3 ± 3.2% HLA-DR-). FL and BM CFCs were CD34(+/++), CD38+, and HLA-DR+. However, significantly more FL CFCs were erythroid (40%) than adult BM CFCs (15%), and FL colonies were larger (8111 ± 738 cells/CFC) than BM colonies (3466 ± 272 cells/CFC, p < 0.001). As is seen in adult BM, FL LTC-ICs were CD34(++/+++) CD38-. In contrast to BM LTC-ICs, FL LTC-ICs were almost exclusively CD34(++/+++) HLA-DR+. In addition, a single FL LTC-IC gave rise to >30 CFCs at 5 weeks compared with only 5 ± 0.9 CFCs per LTC-IC from BM. Finally, we demonstrate that the FL CD34(++/+++)/CD38-/HLA-DR+ population, which contains 3.7% LTC-ICs, also contains primitive lymphoid progenitors capable of differentiating into natural killer (NK) cells. In conclusion, the phenotype of primitive human FL progenitors such as LTC-IC and primitive NK progenitors is CD34(++/+++)/CD38-/HLA-DR+, suggesting that this population may contain FL hematopoietic stem cells. The phenotypic characterization of FL primitive LTC-ICs and NK progenitors will facilitate further studies of the functional properties of these progenitors.

Original languageEnglish (US)
Pages (from-to)387-394
Number of pages8
JournalExperimental Hematology
Volume25
Issue number5
StatePublished - Jun 11 1997
Externally publishedYes

Fingerprint

HLA-DR Antigens
Liver
Natural Killer Cells
Bone Marrow Cells
Bone Marrow
CD38 Antigens
Cell Culture Techniques
CD34 Antigens
Erythroid Cells
Hematopoietic Stem Cells
Population
Flow Cytometry
Lymphocytes
Phenotype

Keywords

  • Human fetal liver
  • Long-term culture initiating cell
  • Natural killer progenitors
  • Phenotypic characterization
  • Proliferative potential

ASJC Scopus subject areas

  • Hematology
  • Molecular Biology
  • Genetics
  • Cell Biology
  • Cancer Research

Cite this

Phenotypic and functional characterization of committed and primitive myeloid and lymphoid hematopoietic precursors in human fetal liver. / Roy, Vivek; Miller, J. S.; Verfaille, C. M.

In: Experimental Hematology, Vol. 25, No. 5, 11.06.1997, p. 387-394.

Research output: Contribution to journalArticle

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abstract = "We studied the phenotypic and functional properties of colony-forming cells (CFCs), primitive long-term culture initiating cells (LTC-ICs) and lymphoid precursors present in human fetal liver (FL) and compared these with their adult bone marrow (BM) counterparts. FL (7-14-week) cells were selected by fluorescence-activated cell sorting based on increasing CD34 antigen expression (34+, 34++, or 34+++), CD38 antigen expression (CD34(++/+++)CD38+, or CD38-), and HLA-DR antigen expression (CD34(++/+++)HLA-DR+ or HLA-DR-). 13 ± 0.6{\%} of FL CD34-positive cells were 34+++. Significantly more FL CD34(++/+++) cells were CD38- (49 ± 2.4{\%}) and HLA-DR- (72 ± 6.7{\%}) than BM CD34++ cells (6.8 ± 0.7{\%} CD38- and 13.3 ± 3.2{\%} HLA-DR-). FL and BM CFCs were CD34(+/++), CD38+, and HLA-DR+. However, significantly more FL CFCs were erythroid (40{\%}) than adult BM CFCs (15{\%}), and FL colonies were larger (8111 ± 738 cells/CFC) than BM colonies (3466 ± 272 cells/CFC, p < 0.001). As is seen in adult BM, FL LTC-ICs were CD34(++/+++) CD38-. In contrast to BM LTC-ICs, FL LTC-ICs were almost exclusively CD34(++/+++) HLA-DR+. In addition, a single FL LTC-IC gave rise to >30 CFCs at 5 weeks compared with only 5 ± 0.9 CFCs per LTC-IC from BM. Finally, we demonstrate that the FL CD34(++/+++)/CD38-/HLA-DR+ population, which contains 3.7{\%} LTC-ICs, also contains primitive lymphoid progenitors capable of differentiating into natural killer (NK) cells. In conclusion, the phenotype of primitive human FL progenitors such as LTC-IC and primitive NK progenitors is CD34(++/+++)/CD38-/HLA-DR+, suggesting that this population may contain FL hematopoietic stem cells. The phenotypic characterization of FL primitive LTC-ICs and NK progenitors will facilitate further studies of the functional properties of these progenitors.",
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N2 - We studied the phenotypic and functional properties of colony-forming cells (CFCs), primitive long-term culture initiating cells (LTC-ICs) and lymphoid precursors present in human fetal liver (FL) and compared these with their adult bone marrow (BM) counterparts. FL (7-14-week) cells were selected by fluorescence-activated cell sorting based on increasing CD34 antigen expression (34+, 34++, or 34+++), CD38 antigen expression (CD34(++/+++)CD38+, or CD38-), and HLA-DR antigen expression (CD34(++/+++)HLA-DR+ or HLA-DR-). 13 ± 0.6% of FL CD34-positive cells were 34+++. Significantly more FL CD34(++/+++) cells were CD38- (49 ± 2.4%) and HLA-DR- (72 ± 6.7%) than BM CD34++ cells (6.8 ± 0.7% CD38- and 13.3 ± 3.2% HLA-DR-). FL and BM CFCs were CD34(+/++), CD38+, and HLA-DR+. However, significantly more FL CFCs were erythroid (40%) than adult BM CFCs (15%), and FL colonies were larger (8111 ± 738 cells/CFC) than BM colonies (3466 ± 272 cells/CFC, p < 0.001). As is seen in adult BM, FL LTC-ICs were CD34(++/+++) CD38-. In contrast to BM LTC-ICs, FL LTC-ICs were almost exclusively CD34(++/+++) HLA-DR+. In addition, a single FL LTC-IC gave rise to >30 CFCs at 5 weeks compared with only 5 ± 0.9 CFCs per LTC-IC from BM. Finally, we demonstrate that the FL CD34(++/+++)/CD38-/HLA-DR+ population, which contains 3.7% LTC-ICs, also contains primitive lymphoid progenitors capable of differentiating into natural killer (NK) cells. In conclusion, the phenotype of primitive human FL progenitors such as LTC-IC and primitive NK progenitors is CD34(++/+++)/CD38-/HLA-DR+, suggesting that this population may contain FL hematopoietic stem cells. The phenotypic characterization of FL primitive LTC-ICs and NK progenitors will facilitate further studies of the functional properties of these progenitors.

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