CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia.
J Cell Mol Med. 2021 Sep;25(18):8701-8714. doi: 10.1111/jcmm.16826. Epub 2021 Aug 2.
To improve the recapitulative quality of human pluripotent stem cell (hPSC) differentiation, we removed exogenous haematopoietic cytokines from the defined differentiation system. Here, we show that endogenous stimuli and VEGF are sufficient to induce robust hPSC-derived haematopoiesis, intensive generation of haematopoietic progenitors, maturation of blood cells and the emergence of definitive precursor cells including those that phenotypically identical to early human embryonic haematopoietic stem cells (HSCs). Moreover, the cytokine-free system produces significantly higher numbers of haematopoietic progenitors compared to the published protocols. The removal of cytokines revealed a broad developmental potential of the early blood cells, stabilized the hPSC-derived definitive precursors and led to spontaneous activation of inflammatory signalling. Our cytokine-free protocol is simple, efficient, reproducible and applicable for embryonic stem cells (ESCs) and induced PSCs. The spectrum of recapitulative features of the novel protocol makes the cytokine-free differentiation a preferred model for studying the early human haematopoietic development.
为了提高人类多能干细胞(hPSC)分化的概括质量,我们从定义明确的分化系统中去除了外源性造血细胞因子。在这里,我们表明内源性刺激物和 VEGF 足以诱导强大的 hPSC 衍生造血作用,大量产生造血祖细胞,使血细胞成熟,并出现明确的前体细胞,包括那些表型与早期人类胚胎造血干细胞(HSCs)相同的前体细胞。此外,无细胞因子系统产生的造血祖细胞数量明显高于已发表的方案。细胞因子的去除揭示了早期血细胞的广泛发育潜力,稳定了 hPSC 衍生的明确前体细胞,并导致炎症信号的自发激活。我们的无细胞因子方案简单、高效、可重复,适用于胚胎干细胞(ESCs)和诱导多能干细胞(iPSCs)。该新方案具有广泛的概括特征,使其成为研究人类早期造血发育的首选模型。