Directed Differentiation of Notochord-like and Nucleus Pulposus-like Cells Using Human Pluripotent Stem Cells | Zendy

Yuelin Zhang | Zendy; Zhao Zhang | Zendy; Peikai Chen | Zendy; Chui Yan | Zendy; Cheng Li | Zendy; Tiffany Y. K. Au | Zendy; Vivian Tam | Zendy; Yan Peng | Zendy; Ron Wu | Zendy; Kmc Cheung | Zendy; Pak C. Sham | Zendy; HungFat Tse | Zendy; Danny Chan | Zendy; Vyl Leung | Zendy; Kathryn S.E. Cheah | Zendy; Qizhou Lian | Zendy

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Directed Differentiation of Notochord-like and Nucleus Pulposus-like Cells Using Human Pluripotent Stem Cells

Author(s) -

Yuelin Zhang,

Zhao Zhang,

Peikai Chen,

Chui Yan,

Cheng Li,

Tiffany Y. K. Au,

Vivian Tam,

Yan Peng,

Ron Wu,

Kmc Cheung,

Pak C. Sham,

HungFat Tse,

Danny Chan,

Vyl Leung,

Kathryn S.E. Cheah,

Qizhou Lian

Publication year - 2020

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2020.01.100

Subject(s) - brachyury , notochord , microbiology and biotechnology , induced pluripotent stem cell , biology , stem cell , cellular differentiation , wnt signaling pathway , transcriptome , embryonic stem cell , sox2 , mesoderm , gene , gene expression , embryo , genetics , signal transduction , embryogenesis

Intervertebral disc degeneration might be amenable to stem cell therapy, but the required cells are scarce. Here, we report the development of a protocol for directed in vitro differentiation of human pluripotent stem cells (hPSCs) into notochord-like and nucleus pulposus (NP)-like cells of the disc. The first step combines enhancement of ACTIVIN/NODAL and WNT and inhibition of BMP pathways. By day 5 of differentiation, hPSC-derived cells express notochordal cell characteristic genes. After activating the TGF-β pathway for an additional 15 days, qPCR, immunostaining, and transcriptome data show that a wide array of NP markers are expressed. Transcriptomically, the in vitro-derived cells become more like in vivo adolescent human NP cells, driven by a set of influential genes enriched with motifs bound by BRACHYURY and FOXA2, consistent with an NP cell-like identity. Transplantation of these NP-like cells attenuates fibrotic changes in a rat disc injury model of disc degeneration.

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