期刊
CELL
卷 133, 期 2, 页码 250-264出版社
CELL PRESS
DOI: 10.1016/j.cell.2008.03.028
关键词
-
资金
- Howard Hughes Medical Institute Funding Source: Medline
- NCI NIH HHS [R37 CA084198, R37 CA084198-08, 5-R37-CA084198, 5-R01-CA087869, R01 CA087869] Funding Source: Medline
- NICHD NIH HHS [R01 HD045022, R01 HD045022-05] Funding Source: Medline
- NIGMS NIH HHS [T32 GM007753] Funding Source: Medline
- PHS HHS [5-R01-HDO45022] Funding Source: Medline
Pluripotent cells can be derived from fibroblasts by ectopic expression of defined transcription factors. A fundamental unresolved question is whether terminally differentiated cells can be reprogrammed to pluripotency. We utilized transgenic and inducible expression of four transcription factors (Oct4, Sox2, Klf4, and c-Myc) to reprogram mouse B lymphocytes. These factors were sufficient to convert nonterminally differentiated B cells to a pluripotent state. However, reprogramming of mature B cells required additional interruption with the transcriptional state maintaining B cell identity by either ectopic expression of the myeloid transcription factor CCAAT/enhancer-binding-protein-alpha (C/EBP alpha) or specific knockdown of the B cell transcription factor Pax5. Multiple iPS lines were clonally derived from both nonfully and fully differentiated B lymphocytes, which gave rise to adult chimeras with germline contribution, and to late-term embryos when injected into tetraploid blastocysts. Our study provides definite proof for the direct nuclear reprogramming of terminally differentiated adult cells to pluripotency.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据