Erasmus Medical Center Stem Cell Institute, Department of Cell Biology, Erasmus Medical Center, Rotterdam, the Netherlands; Centre for Inflammation Research, Queens Medical Research Institute, University of Edinburgh, Edinburgh, UK.
Centre for Inflammation Research, Queens Medical Research Institute, University of Edinburgh, Edinburgh, UK.
Stem Cell Reports. 2018 Jan 9;10(1):151-165. doi: 10.1016/j.stemcr.2017.11.018. Epub 2017 Dec 21.
In vivo hematopoietic generation occurs in waves of primitive and definitive cell emergence. Differentiation cultures of pluripotent embryonic stem cells (ESCs) offer an accessible source of hematopoietic cells for blood-related research and therapeutic strategies. However, despite many approaches, it remains a goal to robustly generate hematopoietic progenitor and stem cells (HP/SCs) in vitro from ESCs. This is partly due to the inability to efficiently promote, enrich, and/or molecularly direct hematopoietic emergence. Here, we use Gata2Venus (G2V) and Ly6a(SCA1)GFP (LG) reporter ESCs, derived from well-characterized mouse models of HP/SC emergence, to show that during in vitro differentiation they report emergent waves of primitive hematopoietic progenitor cells (HPCs), definitive HPCs, and B-lymphoid cell potential. These results, facilitated by enrichment of single and double reporter cells with HPC properties, demonstrate that in vitro ESC differentiation approximates the waves of hematopoietic cell generation found in vivo, thus raising possibilities for enrichment of rare ESC-derived HP/SCs.
体内造血发生是原始和定型细胞出现的波浪式过程。多能胚胎干细胞（ESCs）的分化培养为血液相关研究和治疗策略提供了可获得的造血细胞来源。然而，尽管有许多方法，但从 ESCs 中在体外大量生成造血祖细胞和干细胞（HP/SC）仍然是一个目标。这部分是由于不能有效地促进、富集和/或在分子水平上指导造血出现。在这里，我们使用 Gata2Venus（G2V）和 Ly6a（SCA1）GFP（LG）报告 ESCs，它们源自 HP/SC 出现的经过良好表征的小鼠模型，表明在体外分化过程中，它们报告了原始造血祖细胞（HPC）、定型 HPC 和 B 淋巴细胞潜能的出现波浪。这些结果通过富集具有 HPC 特性的单和双报告细胞得以实现，表明体外 ESC 分化与体内发现的造血细胞生成波浪相似，从而为富集罕见的 ESC 衍生 HP/SC 提供了可能性。
