SALL3 Mediates the Loss of Neuroectodermal Differentiation Potential in Human Embryonic Stem Cells with Chromosome 18q Loss

Overview

Journal Stem Cell Reports

Publisher Cell Press

Specialty Cell Biology

Date 2024 Mar 29

PMID 38552632

Authors

Yingnan Lei

Diana Al Delbany

Nusa Krivec

Marius Regin

Edouard Couvreu de Deckersberg

Charlotte Janssens

Manjusha Ghosh

Karen Sermon

Claudia Spits

Affiliations

Soon will be listed here.

Abstract

Human pluripotent stem cell (hPSC) cultures are prone to genetic drift, because cells that have acquired specific genetic abnormalities experience a selective advantage in vitro. These abnormalities are highly recurrent in hPSC lines worldwide, but their functional consequences in differentiating cells are scarcely described. In this work, we show that the loss of chromosome 18q impairs neuroectoderm commitment and that downregulation of SALL3, a gene located in the common 18q loss region, is responsible for this failed neuroectodermal differentiation. Knockdown of SALL3 in control lines impaired differentiation in a manner similar to the loss of 18q, and transgenic overexpression of SALL3 in hESCs with 18q loss rescued the differentiation capacity of the cells. Finally, we show that loss of 18q and downregulation of SALL3 leads to changes in the expression of genes involved in pathways regulating pluripotency and differentiation, suggesting that these cells are in an altered state of pluripotency.

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