A Quantitative Proteomic Analysis of Hemogenic Endothelium Reveals Differential Regulation of Hematopoiesis by SOX17.

Abstract:

:The in vitro derivation of hematopoietic stem cells (HSCs) from pluripotent stem cells (PSCs) is complicated by the existence of multiple overlapping embryonic blood cell programs called primitive, erythromyeloid progenitor (EMP), and definitive. As HSCs are only generated during the definitive stage of hematopoiesis, deciphering the regulatory pathways that control the emergence of this program and identifying markers that distinguish it from the other programs are essential. To identify definitive specific pathways and marker sets, we used label-free proteomics to determine the proteome of embryo-derived and mouse embryonic stem cell-derived VE-CADHERIN(+)CD45(-) definitive hematopoietic progenitors. With this approach, we identified Stat1 as a marker that distinguishes the definitive erythroid lineage from the primitive- and EMP-derived lineages. Additionally, we provide evidence that the generation of the Stat1(+) definitive lineage is dependent on Sox17. These findings establish an approach for monitoring the emergence of definitive hematopoiesis in the PSC differentiation cultures.

journal_name

Stem Cell Reports

journal_title

Stem cell reports

authors

Clarke RL,Robitaille AM,Moon RT,Keller G

doi

10.1016/j.stemcr.2015.07.008

subject

Has Abstract

pub_date

2015-08-11 00:00:00

pages

291-304

issue

2

issn

2213-6711

pii

S2213-6711(15)00214-3

journal_volume

5

pub_type

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