Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, USA; Bakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA, USA.
Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Cell Rep. 2021 Jan 5;34(1):108573. doi: 10.1016/j.celrep.2020.108573.
Whereas the human fetal immune system is poised to generate immune tolerance and suppress inflammation in utero, an adult-like immune system emerges to orchestrate anti-pathogen immune responses in post-natal life. It has been posited that cells of the adult immune system arise as a discrete ontological "layer" of hematopoietic stem-progenitor cells (HSPCs) and their progeny; evidence supporting this model in humans has, however, been inconclusive. Here, we combine bulk and single-cell transcriptional profiling of lymphoid cells, myeloid cells, and HSPCs from fetal, perinatal, and adult developmental stages to demonstrate that the fetal-to-adult transition occurs progressively along a continuum of maturity-with a substantial degree of inter-individual variation at the time of birth-rather than via a transition between discrete waves. These findings have important implications for the design of strategies for prophylaxis against infection in the newborn and for the use of umbilical cord blood (UCB) in the setting of transplantation.
虽然人类胎儿的免疫系统已经准备好产生免疫耐受和抑制子宫内的炎症，但在出生后，一个类似成人的免疫系统会出现，以协调抗病原体的免疫反应。有人假设，成人免疫系统的细胞是作为一个离散的本体“层”造血干细胞-祖细胞（HSPC）及其后代而出现的；然而，支持这一模型的证据在人类中并不明确。在这里，我们结合了来自胎儿、围产期和成人发育阶段的淋巴细胞、髓细胞和 HSPC 的批量和单细胞转录谱分析，证明胎儿到成人的过渡是沿着一个连续的成熟度进行的——在出生时存在相当大的个体间差异——而不是通过离散波之间的过渡。这些发现对预防新生儿感染的策略设计以及在移植背景下使用脐带血（UCB）具有重要意义。
