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Recapitulative haematopoietic development of human pluripotent stem cells in the absence of exogenous haematopoietic cytokines.

ABSTRACT: 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.

SUBMITTER: Philonenko ES

PROVIDER: S-EPMC8435420 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Recapitulative hematopoietic development of human pluripotent stem cells in the absence of exogenous cytokines

Project description:We tested whether the sustained hematopoietic differentiation of hPSCs can be achieved in defined cell culture conditions without addition of hematopoietic cytokines. Here we show that the endogenous stimuli were sufficient to induce a robust generation of clonogenic hematopoietic progenitors, maturation of blood cells, emergence of the definitive cell lineages, and progenitors that were phenotypically identical to early human embryonic hematopoietic stem cells (HSCs). Our novel cytokine-free protocol is efficient, reproducible, and can be applied for hematopoietic differentiation of human induced pluripotent stem cells (hiPSCs) and embryonic stem cells (hESCs). The removal of cytokines from the differentiation led to detecting a vast developmental potential of the early human blood cells. We also found that the cytokine-free hematopoietic differentiation of hPSCs is associated with strong activation of hPSC-derived inflammatory cells. The spectrum of recapitulative features of the novel protocol makes the cytokine-free differentiation a preferred model for studying early human hematopoietic development

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Recapitulative hematopoietic development of human pluripotent stem cells in the absence of exogenous cytokines

Project description:Recapitulative hematopoietic development of human pluripotent stem cells in the absence of exogenous cytokines

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