Cross-organ HSC trafficking during definitive hematopoiesis formation

在这项研究中，研究了胚胎到新生小鼠造血形成过程中造血干细胞（HSC）运输的细胞和分子机制。从骨髓、肝脏和脾脏分离的P2造血干细胞的单细胞rna测序显示了造血干细胞的异质性。PCA分析显示3个不同的HSC簇具有独特的HSC标记表达（不同水平的cKit、Sca-1、CD150平均荧光强度）和差异表达基因。我们通过体外CFU-F和体内10细胞移植到致死辐照小鼠的功能分析显示，这3组在产生菌落和供体嵌合的能力上存在显著差异。我们现在正在通过谱系追踪和敲除或敲除研究来研究这些HSC群的生物学意义及其对成人造血的贡献。

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.