华盛顿大学医学院的Jeffrey A. Magee小组取得新进展。研究人员揭示了出生前就开始的逐步和不协调的转录重编程。 相关论文于2020年8月20号发表在《细胞—干细胞》杂志上。

研究显示小鼠造血干细胞（HSC）和造血祖细胞（HPC）从胎儿到成人的转录状态经历了逐渐而不是突然的转变。过渡期始于出生前，并因产前晚期I型干扰素信号转导而中断，从而促进围产期HPC扩展并使祖细胞对致白血病的FLT3ITD突变敏感。基因表达和增强子激活中的大多数其他变化时间不精确且协调性差。因此，异时增强子元件及其相关的转录本彼此独立地而不是作为鲁棒网络的一部分被激活。这简化了指导新生儿HSC / HPC个体发育的监管程序，但它创造了这些人群中的异质性。

据了解，胎儿和造血干细胞（HSC）具有不同的增殖率、谱系偏倚、基因表达谱和基因依赖性。尽管这些差异得到了广泛认可，但尚不清楚如何协调从胎儿身份到成人身份的过渡。

附：英文原文

Title: Single-Cell Analysis of Neonatal HSC Ontogeny Reveals Gradual and Uncoordinated Transcriptional Reprogramming that Begins before Birth

Author: Yanan Li, Wenjun Kong, Wei Yang, Riddhi M. Patel, Emily B. Casey, Theresa Okeyo-Owuor, J. Michael White, Shaina N. Porter, Samantha A. Morris, Jeffrey A. Magee

Issue&Volume: 2020-08-20

Abstract: Fetal and adult hematopoietic stem cells (HSCs) have distinct proliferation rates,lineage biases, gene expression profiles, and gene dependencies. Although these differencesare widely recognized, it is not clear how the transition from fetal to adult identityis coordinated. Here we show that murine HSCs and committed hematopoietic progenitorcells (HPCs) undergo a gradual, rather than precipitous, transition from fetal toadult transcriptional states. The transition begins prior to birth and is punctuatedby a late prenatal spike in type I interferon signaling that promotes perinatal HPCexpansion and sensitizes progenitors to the leukemogenic FLT3ITD mutation. Most other changes in gene expression and enhancer activation are impreciselytimed and poorly coordinated. Thus, heterochronic enhancer elements, and their associatedtranscripts, are activated independently of one another rather than as part of a robustnetwork. This simplifies the regulatory programs that guide neonatal HSC/HPC ontogeny,but it creates heterogeneity within these populations.

DOI: 10.1016/j.stem.2020.08.001

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30397-0