Cross-organ HSC trafficking during definitive hematopoiesis formation

在这项研究中，造血干细胞（HSC）运输的细胞和分子机制，发生在确定的造血形成在胎儿到新生小鼠进行了调查。从骨髓、肝脏和脾脏分离的P2 HSC的单细胞RNA测序揭示了HSC异质性。PCA分析显示3个不同的HSC簇具有独特的HSC标志物表达（不同水平的cKit、Sca-1、CD 150平均荧光强度）和差异表达的基因。我们通过体外CFU-F和体内10-细胞移植到致死性照射小鼠的功能分析显示，这3组在产生集落和供体嵌合体的能力方面存在显著差异。我们现在正在研究这些HSC群的生物学意义，以及它们通过谱系追踪和敲除或敲低研究对成人造血的贡献。

In this study, the cellular and molecular mechanism of hematopoietic stem cell (HSC) trafficking that occurs during definitive hematopoiesis formation was investigated in the fetal to neonatal mouse. Single-cell RNA-sequencing of P2 HSCs isolated from the bone marrow, liver and spleen revealed HSC heterogeneity. PCA analysis showed 3 distinct clusters of HSCs with unique HSC marker expression (varying levels of cKit, Sca-1, CD150 mean fluorescence intensity) and differentially expressed genes. Our functional analysis via in vitro CFU-F and in vivo 10-cell transplantation into lethally irradiated mice revealed striking differences among these 3 groups in their ability to generate colonies and donor chimerism. We are now investigating the biological significance of these HSC groups and their contribution to adult hematopoiesis via lineage tracing and knock-out or knock-down studies.