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系统单细胞分析揭示了转座元件活性的动态控制，协调内皮细胞向造血细胞的转变。

Systematic single-cell analysis reveals dynamic control of transposable element activity orchestrating the endothelial-to-hematopoietic transition.

机构信息

Department of Bioinformatics, College of Life Sciences, Zhejiang University, Hangzhou, 310058, China.

Bioinformatics Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.

出版信息

BMC Biol. 2024 Jun 27;22(1):143. doi: 10.1186/s12915-024-01939-5.

DOI:10.1186/s12915-024-01939-5
PMID:38937802
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11209969/
Abstract

BACKGROUND

The endothelial-to-hematopoietic transition (EHT) process during definitive hematopoiesis is highly conserved in vertebrates. Stage-specific expression of transposable elements (TEs) has been detected during zebrafish EHT and may promote hematopoietic stem cell (HSC) formation by activating inflammatory signaling. However, little is known about how TEs contribute to the EHT process in human and mouse.

RESULTS

We reconstructed the single-cell EHT trajectories of human and mouse and resolved the dynamic expression patterns of TEs during EHT. Most TEs presented a transient co-upregulation pattern along the conserved EHT trajectories, coinciding with the temporal relaxation of epigenetic silencing systems. TE products can be sensed by multiple pattern recognition receptors, triggering inflammatory signaling to facilitate HSC emergence. Interestingly, we observed that hypoxia-related signals were enriched in cells with higher TE expression. Furthermore, we constructed the hematopoietic cis-regulatory network of accessible TEs and identified potential TE-derived enhancers that may boost the expression of specific EHT marker genes.

CONCLUSIONS

Our study provides a systematic vision of how TEs are dynamically controlled to promote the hematopoietic fate decisions through transcriptional and cis-regulatory networks, and pre-train the immunity of nascent HSCs.

摘要

背景

在定型造血过程中，内皮细胞向造血细胞的转变（EHT）过程在脊椎动物中高度保守。在斑马鱼 EHT 过程中检测到转座元件（TEs）的阶段特异性表达，通过激活炎症信号可能促进造血干细胞（HSC）的形成。然而，关于 TEs 如何在人类和小鼠中促进 EHT 过程知之甚少。

结果

我们重建了人类和小鼠的单细胞 EHT 轨迹，并解析了 EHT 过程中 TEs 的动态表达模式。大多数 TEs 沿着保守的 EHT 轨迹呈现出短暂的共上调模式，与表观遗传沉默系统的时间放松一致。TE 产物可以被多种模式识别受体感知，从而触发炎症信号以促进 HSC 的出现。有趣的是，我们观察到与缺氧相关的信号在 TE 表达较高的细胞中富集。此外，我们构建了可及 TEs 的造血顺式调控网络，并鉴定了可能增强特定 EHT 标记基因表达的潜在 TE 衍生增强子。

结论

我们的研究提供了一个系统的视角，说明 TEs 是如何通过转录和顺式调控网络动态控制来促进造血命运决定，并预先训练新生 HSCs 的免疫。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/030e/11209969/fd84be8612ab/12915_2024_1939_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/030e/11209969/cc0630679cc9/12915_2024_1939_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/030e/11209969/bdd5d2061d18/12915_2024_1939_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/030e/11209969/0997da14ef51/12915_2024_1939_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/030e/11209969/ecbaaee7f231/12915_2024_1939_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/030e/11209969/ab0117a1e7f8/12915_2024_1939_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/030e/11209969/6de4108fc5c5/12915_2024_1939_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/030e/11209969/fd84be8612ab/12915_2024_1939_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/030e/11209969/cc0630679cc9/12915_2024_1939_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/030e/11209969/145ba48ff106/12915_2024_1939_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/030e/11209969/983934d5569a/12915_2024_1939_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/030e/11209969/bdd5d2061d18/12915_2024_1939_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/030e/11209969/0997da14ef51/12915_2024_1939_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/030e/11209969/ecbaaee7f231/12915_2024_1939_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/030e/11209969/ab0117a1e7f8/12915_2024_1939_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/030e/11209969/6de4108fc5c5/12915_2024_1939_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/030e/11209969/fd84be8612ab/12915_2024_1939_Fig9_HTML.jpg

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