single-cell analysis of murine long-term hematopoietic stem cells reveals distinct patterns of gene expression during fetal migration单细胞分析小鼠长期造血干细胞揭示胎儿迁移期间不同的基因表达模式.pdfVIP
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single-cell analysis of murine long-term hematopoietic stem cells reveals distinct patterns of gene expression during fetal migration单细胞分析小鼠长期造血干细胞揭示胎儿迁移期间不同的基因表达模式
Single-Cell Analysis of Murine Long-Term Hematopoietic
Stem Cells Reveals Distinct Patterns of Gene Expression
during Fetal Migration
´ ´
Jesus Ciriza, Dominique Hall, Alison Lu, Joseph Robert De Sena, Mufadhal Al-Kuhlani, Marcos E. Garcıa-
Ojeda*
School of Natural Sciences, University of California Merced, Merced, California, United States of America
Abstract
Background: Long-term hematopoietic stem cells (LT-HSCs) migrate from the fetal liver (FL) to the fetal bone marrow (FBM)
during development. Various adhesion and chemotactic receptor genes have been implicated in the migration of adult LT-
HSCs. However, their role in the migration of fetal LT-HSCs is not clearly understood due, in part, to the rare number of these
cells in fetal tissues, which preclude classical gene expression analysis. The aim of this study is to characterize the expression
of migration related genes in fetal LT-HSC across different anatomical locations during development.
Methodology/Principal Findings: We isolated fetal LT-HSC from different developmental stages, as well as different
anatomical locations, and performed single-cell multiplex RT-qPCR and flow cytometry analysis of eight molecules involved
in adult LT-HSC migration. Our results show that the gene expression of the chemokine receptor Cxcr4 in LT-HSC varies
across developmental microenvironments and times, while the cadherin Cdh2 (Ncad) and the calcium receptor Casr show
higher gene expression and variability only in FBM at 17.5 days post coitum (dpc). The cadherin Cdh5 (Vecad) maintains high
expression variability only during fetal development, while the integrin subunit Itga5 (a5) increases its variability after 14.5
dpc. The integrin subunits Itga4 (a4) and
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