德国马克斯•普朗克免疫生物学与表观遗传学研究所Rudolf Grosschedl和Marta Derecka研究组合作取得一项新成果。他们的研究发现缺乏EBF1的骨髓基质引发造血干细胞（HSC）潜能性持续变化。该项研究成果在线发表在2020年2月17日的《自然-免疫学》上。

研究人员探究了骨髓（BM）间充质基质细胞（MSC）的转录变化对HSC的长期影响。对Cxcl12丰富的网状（CAR）细胞和PDGFRα⁺ Sca1 ⁺（PαS）细胞的单细胞分析显示出广泛的细胞异质性，但两者都表达转录因子Ebf1。

在MSC中条件性敲除Ebf1改变了它们的细胞组成、染色质结构和基因表达谱，包括粘附相关基因的表达减少。在功能上，基质特异性Ebf1失活导致HSC的粘附受损，从而导致静息性降低和骨髓输出减少。最值得注意的是，Ebf1缺陷的驻留HSC其细胞组成和染色质结构发生了变化，这些变化在连续移植中仍然存在。因此，BM小生境中的遗传改变会导致HSC的长期功能改变。

据介绍，间充质基质细胞（MSC）与造血干细胞（HSC）之间的相互作用对造血稳态和血统输出至关重要。

附：英文原文

Title: EBF1-deficient bone marrow stroma elicits persistent changes in HSC potential

Author: Marta Derecka, Josip Stefan Herman, Pierre Cauchy, Senthilkumar Ramamoorthy, Ekaterina Lupar, Dominic Grn, Rudolf Grosschedl

Issue&Volume: 2020-02-17

Abstract: Crosstalk between mesenchymal stromal cells (MSCs) and hematopoietic stem cells (HSCs) is essential for hematopoietic homeostasis and lineage output. Here, we investigate how transcriptional changes in bone marrow (BM) MSCs result in long-lasting effects on HSCs. Single-cell analysis of Cxcl12-abundant reticular (CAR) cells and PDGFRα+Sca1+ (PαS) cells revealed an extensive cellular heterogeneity but uniform expression of the transcription factor gene Ebf1. Conditional deletion of Ebf1 in these MSCs altered their cellular composition, chromatin structure and gene expression profiles, including the reduced expression of adhesion-related genes. Functionally, the stromal-specific Ebf1 inactivation results in impaired adhesion of HSCs, leading to reduced quiescence and diminished myeloid output. Most notably, HSCs residing in the Ebf1-deficient niche underwent changes in their cellular composition and chromatin structure that persist in serial transplantations. Thus, genetic alterations in the BM niche lead to long-term functional changes of HSCs.

DOI: 10.1038/s41590-020-0595-7

Source: https://www.nature.com/articles/s41590-020-0595-7