Akashi Koichi
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.
Ann N Y Acad Sci. 2005 Jun;1044:125-31. doi: 10.1196/annals.1349.016.
Hematopoiesis has provided a valuable model for understanding how genetic programs are established to decide cell fates in multipotent stem or progenitor cells. The identification of common myeloid and lymphoid progenitors has allowed us to directly assess the regulatory mechanisms of lineage commitment. Multiple genes of hematopoietic lineages, including transcription factors, are coexpressed in hematopoietic stem cells and progenitors, a phenomenon referred to as "lineage priming." The accessibility for multiple transcription factors promiscuously allows flexibility in cell fate commitments at the multipotent stages. The changes in the expression levels and timing of transcription factors can induce lineage conversion of committed cells, indicating that the regulation of transcription factors might be primarily critical for maintaining hierarchical hematopoietic development.
造血作用为理解如何建立遗传程序以决定多能干细胞或祖细胞的细胞命运提供了一个有价值的模型。常见髓系和淋巴系祖细胞的鉴定使我们能够直接评估谱系定向的调控机制。包括转录因子在内的多个造血谱系基因在造血干细胞和祖细胞中共同表达,这一现象被称为“谱系预激发”。多个转录因子的可及性允许在多能阶段细胞命运定向具有灵活性。转录因子表达水平和时间的变化可诱导定向细胞的谱系转换,这表明转录因子的调控可能对维持分层造血发育至关重要。