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Dysregulated Gene Expression During Hematopoietic Differentiation From HESC
4 k. |) E- x! q8 m8 L9 C原文来自于% r; k0 t: k* j. k, e
http://www.nature.com/mt/journal ... ull/mt2010281a.html
( z9 _' r' ~ F( A% O4 n由干细胞之家新闻小组成员Hyde翻译（转帖请注明）
( ?6 f0 A0 `/ e( z( U9 c1 vGautam Dravid, Yuhua Zhu, Jessica Scholes, Denis Evseenko and Gay M Crooks
) f. B9 x( M- G' f: V* E% e5 \ \* `* r) C
使用hESC诱导成造血干细胞提高了使用hESC作为可选的供体来源用于移植的可能性。但是使用hESC诱导的细胞存在的功能性缺陷限制了其在淋巴造血重建方面的应用。现在的研究目的在于明确和定量分析不同来源（hESC 和脐带血）的CD34+（造血前体细胞）在主要功能和分子上的区别。使用hESC诱导中胚层形成了两个亚群的CD34细胞，CD34bright 有造血活性、CD34dim造血功能抑制。极限稀释分析发现相比于脐带血来源的细胞，hESC来源的细胞克隆具有一些缺陷，特别是B淋巴条件（？）。在UCB-CD34+ cells 发育为B淋巴的过程中的特定阶段表达的转录因子在 hESC-derived CD34+ cells中出现了畸形的表达。另外，负调节淋巴生成的因子如the adaptor protein LNK and CCAAT/enhancer-binding protein-α (CEBPα)在hESC-CD34+ subsets中高度表达。降低表达LNK 能够增加hESCs来源的造血前体细胞的效率。在hESC-CD34+ cells 中异常表达的分子持续转录，首次表达在未分化的hESC和中胚层前体细胞，可能是从hESc到造血干细胞的障碍（这句话不太理解，sorry）。' Y, [0 A2 `7 P* ?$ N
% v [0 X5 \* [6 G5 N! QThe generation of hematopoietic cells from human embryonic stem cells (hESC) has raised the possibility of using hESC as an alternative donor source for transplantation. However, functional defects identified in hESC-derived cells limit their use for full lymphohematopoietic reconstitution. The purpose of the present study was to define and quantitate key functional and molecular differences between CD34+ hematopoietic progenitor subsets derived from hESC and CD34+ subsets from umbilical cord blood (UCB) representing definitive hematopoiesis. Two distinct sub-populations were generated following mesodermal differentiation from hESC, a CD34bright (hematoendothelial) and CD34dim (hematopoietic-restricted) subset. Limiting dilution analysis revealed profound defects in clonal proliferation relative to UCB particularly in B lymphoid conditions. Transcription factors normally expressed at specific commitment stages during B lymphoid development from UCB-CD34+ cells were aberrantly expressed in hESC-derived CD34+ cells. Moreover, strong negative regulators of lymphopoiesis such as the adaptor protein LNK and CCAAT/enhancer-binding protein-α (CEBPα), were exclusively expressed in hESC-CD34+ subsets. Knockdown of LNK lead to an increase in hematopoietic progenitors generated from hESCs. The aberrant molecular profile seen in hESC-CD34+ cells represents persistence of transcripts first expressed in undifferentiated hESC and/or CD326-CD56+ mesoderm progenitors, and may contribute to the block in definitive hematopoiesis from hESC.; i6 K% _9 N9 n+ q b5 u7 ?% y3 }
! p# H7 a( |, I! q8 J注明：个人翻译，理解不准确的语句还望大家积极指出。 |
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发表于 2010-12-27 16:07
