Developmental plasticity of lymphocytes.
Experimental perturbation of signaling or transcription factor networks has been used to study the developmental potential of lymphoid progenitors, lineage-committed precursors and mature lymphocytes. Common lymphoid progenitors and uncommitted pro-T cells can be efficiently diverted into myeloid or erythroid lineages by ectopic cytokine signaling or retroviral expression of the myeloid C/EBPalpha or erythroid GATA1 transcription factor. Forced C/EBPalpha expression furthermore induces direct transdifferentiation of immature thymocytes or B cells into macrophages. Notably, conditional inactivation of the B cell commitment factor Pax5 is sufficient to convert mature B cells into functional T cells via dedifferentiation to uncommitted progenitors. Together these experiments have uncovered an unanticipated developmental plasticity of lymphocytes, which may account for lineage switches observed in human malignancies.
Cobaleda
César
C
Universidad de Salamanca, Campus Miguel de Unamuno, 37007 Salamanca, Spain.
Busslinger
Meinrad
M
D054337:Cell Dedifferentiation; D002454:Cell Differentiation; D019070:Cell Lineage; D016207:Cytokines / Q000502:physiology; D019337:Hematologic Neoplasms / Q000235:genetics; D006801:Humans; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D054504:Precursor Cells, T-Lymphoid / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism
D016207:Cytokines; D014157:Transcription Factors