Tissue source dictates lineage outcome of human fetal CD34(+)CD38(-) cells.
OBJECTIVE
The translocation from fetal liver hematopoiesis to secondary organs occurs during the second trimester of human gestation. It has been hypothesized that stem cells migrate and acquire lineage potential based on cues specific to the adopted microenvironment. We evaluated primitive hematopoietic cell populations in the fetal human to determine if lineage restriction precedes or follows translocation to sites of hematopoietic activity including thymus, spleen, bone marrow, and liver.


METHODS
Sets of hematopoietic tissues from individual second-trimester human abortuses were used to compare and quantitate the lineage outcome of immunophenotypically primitive cells from each of the hematopoietic organs using ex vivo myeloid and lymphoid differentiation systems.


RESULTS
Despite uniformity in immunophenotype, functional capabilities were highly restricted by the tissue of origin and alteration in the ex vivo differentiation context did not lead to a change in differentiation outcome.


CONCLUSIONS
Translocation of primitive cells from fetal liver to tissues of mature hematopoietic activity is associated with tissue-specific, quantitative changes in differentiation potential that are unresponsive to alternative differentiation environments. These data suggest that multipotentiality is lost prior to or upon stem-cell migration in the developing human. It is not persistent with residence in a secondary hematopoietic organ.
Poznansky
M C
MC
AIDS Research Center and MGH Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, Mass., USA.
Olszak
I T
IT
Foxall
R B
RB
Piascik
A
A
Adams
G B
GB
Evans
R H
RH
Cheng
T
T
Scadden
D T
DT
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000818:Animals; D015703:Antigens, CD / Q000032:analysis*; D018952:Antigens, CD34 / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis; D018929:Cell Culture Techniques / Q000379:methods; D002469:Cell Separation; D002478:Cells, Cultured; D005333:Fetus; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D008099:Liver / Q000166:cytology / Q000196:embryology* / Q000276:immunology; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D009244:NAD+ Nucleosidase / Q000032:analysis; D009928:Organ Specificity; D013154:Spleen / Q000166:cytology / Q000196:embryology* / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology* / Q000276:immunology
D015703:Antigens, CD; D018952:Antigens, CD34; D000943:Antigens, Differentiation; D008562:Membrane Glycoproteins; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; C498155:Cd38 protein, mouse; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1