Clonal analysis of fetal hematopoietic stem/progenitor cells reveals how post-transplantation capabilities are distributed.

IF 5.9 2区医学 Q1 CELL & TISSUE ENGINEERING

Stem Cell Reports Pub Date : 2024-08-13 Epub Date: 2024-08-01 DOI:10.1016/j.stemcr.2024.07.003

Olivia J Stonehouse, Christine Biben, Tom S Weber, Alexandra Garnham, Katie A Fennell, Alison Farley, Antoine F Terreaux, Warren S Alexander, Mark A Dawson, Shalin H Naik, Samir Taoudi

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Abstract

It has been proposed that adult hematopoiesis is sustained by multipotent progenitors (MPPs) specified during embryogenesis. Adult-like hematopoietic stem cell (HSC) and MPP immunophenotypes are present in the fetus, but knowledge of their functional capacity is incomplete. We found that fetal MPP populations were functionally similar to adult cells, albeit with some differences in lymphoid output. Clonal assessment revealed that lineage biases arose from differences in patterns of single-/bi-lineage differentiation. Long-term (LT)- and short-term (ST)-HSC populations were distinguished from MPPs according to capacity for clonal multilineage differentiation. We discovered that a large cohort of long-term repopulating units (LT-RUs) resides within the ST-HSC population; a significant portion of these were labeled using Flt3-cre. This finding has two implications: (1) use of the CD150+ LT-HSC immunophenotype alone will significantly underestimate the size and diversity of the LT-RU pool and (2) LT-RUs in the ST-HSC population have the attributes required to persist into adulthood.

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胎儿造血干细胞/祖细胞的克隆分析揭示了移植后能力的分布情况。

有人提出，成人造血是由胚胎发育过程中指定的多潜能祖细胞（MPPs）维持的。胎儿体内存在类似成人的造血干细胞（HSC）和MPP免疫表型，但对其功能能力的了解还不全面。我们发现，胎儿 MPP 群体在功能上与成人细胞相似，尽管在淋巴输出方面存在一些差异。克隆评估显示，单/双系分化模式的差异导致了系的偏差。长期（LT）和短期（ST）造血干细胞群是根据克隆多系分化能力从多系淋巴细胞中区分出来的。我们发现，ST-造血干细胞群体中有一大批长期再增殖单位（LT-RUs）；其中很大一部分是用 Flt3-cre 标记的。这一发现有两个意义：（1）仅使用 CD150+ LT-HSC 免疫表型会大大低估 LT-RU 库的规模和多样性；（2）ST-HSC 群体中的 LT-RU 具有持续到成年所需的属性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Stem Cell Reports CELL & TISSUE ENGINEERING-CELL BIOLOGY

CiteScore

10.50

自引率

1.70%

发文量

200

审稿时长

28 weeks

期刊介绍： Stem Cell Reports publishes high-quality, peer-reviewed research presenting conceptual or practical advances across the breadth of stem cell research and its applications to medicine. Our particular focus on shorter, single-point articles, timely publication, strong editorial decision-making and scientific input by leaders in the field and a "scoop protection" mechanism are reasons to submit your best papers.