Nat Commun He Aibin's research group reveals the epigenetic inheritance of the origin of hematopoietic stem cells..

On January 17, 2022, He Aibin's research group from Peking University Institute of Molecular Medicine and Life Science Joint Center published a research paper "Pre-configuring chromatin architecture with hisstone modifications guides hematopoietic stem cell formation in mouse embryos" online in the journal Nature Communications.

Hematopoietic stem cells (HSCs) maintain the composition and function of cell populations throughout the hematopoietic system

In order to explore the scientific question of how multi-dimensional epigenetic levels in mammalian embryos regulate the occurrence of HSCs, this study broke through the technical bottleneck of small-scale cell detection and applied a small-scale cell sisHi-C (small-scale in situ Hi-C) technology3 and The small-cell itChIP-seq (indexing and tagmentation-based chromatinimmunoprecipitation sequencing) technology4 developed by He Aibin's team in 2019 detected chromatin interaction structure, histone modification and transcription factor binding maps in hundreds of cells

Figure 1.

Changes in chromatin interactions that promote hematopoiesis occur within topologically associated domains (TADs)

Figure 2.

Surprisingly, it was found that RUNX1 protein was enriched in the anchor region of enhancer-promoter (EP) interaction as early as the eAEC period

Figure 3.

In short, this study breaks through the technical bottleneck of limiting the number of cells in in vivo samples, integrates multi-omics data of multi-level chromatin structure, different histone modifications and transcription factor RUNX1, and reveals the epigenetic-level regulation of HSC origin.

Professor He Aibin, Researcher Liu Bing (The Fifth Medical Center of PLA General Hospital), and Researcher Lan Yu (Jinan University) are the co-corresponding authors of this article

https:// 

references:

1.

2.

3.
Du Z, et al.
Allelic reprogramming of 3D chromatin architecture during early mammalian development.
Nature 547, 232-235(2017).

4.
AiS, et al.
Profiling chromatin states using single-cell itChIP-seq.
Nat CellBiol 21, 1164-1172 (2019).

5.
Chen MJ, Yokomizo T, Zeigler BM, Dzierzak E, Speck NA.
Runx1 is required for the endothelial to haematopoietic cell transition but not thereafter.
Nature 457, 887-891 (2009).

6.
Lacaud G, et al.
Runx1 is essential for hematopoietic commitment at the hemangioblast stage of development in vitro.
Blood 100, 458-466 (2002).

7.
YokomizoT, et al.
Runx1 is involved inprimitive erythropoiesis in the mouse.
Blood 111, 4075-4080 (2008).

8.
Wilson NK, et al.
Combinatorial transcriptional control in blood stem/progenitor cells: genome-wide analysis often major transcriptional regulators.
CellStem Cell 7, 532-544 (2010).

9.
Gilmour J, Assi SA, Noailles L, Lichtinger M, Obier N, Bonifer C.
The Co-operation of RUNX1 with LDB1, CDK9 and BRD4 Drives Transcription Factor Complex Relocation During Haematopoietic Specification.
Sci Rep 8, 10410 (2018).

10.
Nottingham WT, et al.
Runx1-mediated hematopoietic stem-cell emergence is controlled by a Gata/Ets/SCL-regulated enhancer.
Blood 110, 4188-4197 (2007).