Maintenance of Human Haematopoietic Stem and Progenitor Cells in Vitro Using a Chemical Cocktail

Overview

Journal Cell Discov

Date 2018 Nov 6

PMID 30393564

Citations 11

Authors

Mengmeng Jiang

Haide Chen

Shujing Lai

Renying Wang

Yunfei Qiu

Fang Ye

Lijiang Fei

Huiyu Sun

Yang Xu

Xinyi Jiang

Ziming Zhou

Tingyue Zhang

Yanwei Li

Jin Xie

Qun Fang

Robert Peter Gale

Xiaoping Han

He Huang

Guoji Guo

Affiliations

Soon will be listed here.

Abstract

Identification of effective culture conditions to maintain and possibly expand human HSPCs in vitro is an important goal. Recent advances highlight the efficacy of chemicals in maintaining and converting cell fates. We screened 186 chemicals and found that a combination of CHIR-99021, Forskolin and OAC1 (CFO) maintained human CD34-positive cells in vitro. Efficiency of the culture system was characterized using flow cytometry for CD34-positive cells, a colony-forming assay and xeno-transplants. We found that human CD34-positive cells treated with this combination had enhanced expression of human HSPC markers and increased haematopoietic re-populating ability in immune-deficient mice. Single-cell RNA-seq analyses showed that the in vitro cultured human CD34-positive cells were heterogeneous. We found that CFO supports maintenance of human CD34-positive cells by activating , and AKT-cAMP signaling pathway. These data have implications in therapies requiring maintenance and/or expansion of human HSPCs.

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