Open AccessRecapitulative haematopoietic development of human pluripotent stem cells in the absence of exogenous haematopoietic cytokines
Author(s) -
Philonenko Elena S.,
Tan Ying,
Wang Cuihua,
Zhang Baoyun,
Shah Zahir,
Zhang Jianguang,
Ullah Hanif,
Kiselev Sergei L.,
Lagarkova Maria A.,
Li Dandan,
Dai Yong,
Samokhvalov Igor M.
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16826
Subject(s) - haematopoiesis , stem cell , embryonic stem cell , biology , induced pluripotent stem cell , microbiology and biotechnology , progenitor cell , cytokine , immunology , genetics , gene
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.