小柯机器人

美国圣路易斯华盛顿大学Kenneth M. Murphy研究组发现，转录抑制因子Zeb2增强子的不同使用可区分成年造血和胚胎造血。这一研究成果于2021年5月17日在线发表在国际学术期刊《免疫》上。

研究人员确定了一个位于Zeb2转录起始位点（TSS）上游165 kb的400 bp区域，该区域在几个E-box图案上结合E蛋白，并在造血谱系中活跃。此400 bp区域（Zeb2^Δ-165小鼠）的种系缺失特异性阻止了造血干细胞（HSC）衍生谱系中Zeb2的表达。Zeb2^Δ−165小鼠缺乏浆细胞样树突状细胞（pDC）、单核细胞和B细胞的发育。Zeb2^Δ−165小鼠中的所有巨噬细胞都是胚胎来源的。

使用单细胞染色质分析，研究人员确定了位于+164-kb的第二个Zeb2增强子，该增强子在胚胎来源的谱系中具有选择性活性，而在HSC衍生的谱系中则不具有活性。因此，成年造血细胞中的Zeb2表达，而不是胚胎的造血作用，是由–165-kb Zeb2增强子选择性控制的。

据悉，转录抑制因子ZEB2调节体细胞、神经和造血谱系中许多细胞命运的发展，但尚不清楚这些多样化谱系中其需求的基础。

附：英文原文

Title: Differential usage of transcriptional repressor Zeb2 enhancers distinguishes adult and embryonic hematopoiesis

Author: Xiao Huang, Stephen T. Ferris, Sunkyung Kim, Mayank N.K. Choudhary, Julia A. Belk, Changxu Fan, Yanyan Qi, Raki Sudan, Yu Xia, Pritesh Desai, Jing Chen, Nghi Ly, Quanming Shi, Prachi Bagadia, Tiantian Liu, Martin Guilliams, Takeshi Egawa, Marco Colonna, Michael S. Diamond, Theresa L. Murphy, Ansuman T. Satpathy, Ting Wang, Kenneth M. Murphy

Issue&Volume: 2021-05-17

Abstract: The transcriptional repressor ZEB2 regulates development of many cell fates amongsomatic, neural, and hematopoietic lineages, but the basis for its requirement inthese diverse lineages is unclear. Here, we identified a 400-basepair (bp) regionlocated 165 kilobases (kb) upstream of the Zeb2 transcriptional start site (TSS) that binds the E proteins at several E-box motifsand was active in hematopoietic lineages. Germline deletion of this 400-bp region(Zeb2Δ165mice) specifically prevented Zeb2 expression in hematopoietic stem cell (HSC)-derived lineages. Zeb2Δ165 mice lacked development of plasmacytoid dendritic cells (pDCs), monocytes, and Bcells. All macrophages in Zeb2Δ165 mice were exclusively of embryonic origin. Using single-cell chromatin profiling,we identified a second Zeb2 enhancer located at +164-kb that was selectively active in embryonically derivedlineages, but not HSC-derived ones. Thus, Zeb2 expression in adult, but not embryonic, hematopoiesis is selectively controlled bythe –165-kb Zeb2 enhancer.

DOI: 10.1016/j.immuni.2021.04.015

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00177-1

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