Transcriptional regulation of hematopoietic stem cell progenitors and acute myeloid leukemia by the IRE1a-XBP1 pathway [overexpression]. Transcriptional regulation of hematopoietic stem cell progenitors and acute myeloid leukemia by the IRE1a-XBP1 pathway [overexpression]

The inositol-requiring enzyme-1a (IRE1a), through its key effector transcription factor X-box binding protein-1 (XBP1), regulates cell fate and malignancy in a tissue and cell-specific manner. Here, we define the transcriptional perturbations associated with induction of XBP1 (encoded by the XBP1S gene generated by IRE1a) eficiency in patient derived human AML cells. Beyond its classical role in activating genes involved in restoring cellular proteostasis during the unfolded protein response (UPR), our transcriptome analysis reveal XBP1-dependent regulation of genes involved in diverse biological processes required for HSC homeostasis and acute myeloid leukemia (AML) development. Overall design: Transcriptome of two patient-derived human AML cells (#41 and #88) transduced with control lentivirus (in triplicates, C1, C2 and C3) or XBP1 (X1, X2 and X3) were determined using TruSeq Stranded mRNA Libraries. The complete data set contains a total of 12 samples

肌醇需求酶1α（inositol-requiring enzyme-1a, IRE1α）通过其关键效应转录因子X盒结合蛋白1（X-box binding protein-1, XBP1），以组织与细胞特异性的方式调控细胞命运及恶性表型。本研究明确了患者来源的人急性髓系白血病（acute myeloid leukemia, AML）细胞中，由IRE1α剪接产生的XBP1S编码的XBP1功能缺陷所相关的转录扰动。除了在未折叠蛋白反应（unfolded protein response, UPR）中激活参与恢复细胞蛋白质稳态的基因这一经典功能外，我们的转录组分析揭示，XBP1可依赖自身调控造血干细胞（hematopoietic stem cell, HSC）稳态及急性髓系白血病（AML）发生所需的多种生物学过程相关基因。总体实验设计：采用TruSeq链特异性mRNA文库，对两株患者来源的人AML细胞（#41与#88）的转录组进行测序，这些细胞分别被转导了对照慢病毒（设置3个生物学重复：C1、C2、C3）或XBP1过表达载体（设置3个生物学重复：X1、X2、X3）。本完整数据集共计包含12个样本。