Evidence map›Paper›PMID 35349707›Full record

ArticleStem cells translational medicine2022

SAHA Enhances Differentiation of CD34+CD45+ Hematopoietic Stem and Progenitor Cells from Pluripotent Stem Cells Concomitant with an Increase in Hemogenic Endothelium.

Seon-Hui Shim, Dejene Tufa, Renee Woods, Trahan D George, Tyler Shank, Ashley Yingst, Jessica Lake, Laura Cobb, Dallas Jones, Kenneth Jones and 1 more

Open access · goldAbstract read
In one paragraph

Article in Stem cells translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.4field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 14 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 1 country.

Seon-Hui ShimUniversity of Colorado and Children's Hospital of Colorado, Department of Children's Cancer and Blood Disorders, Aurora, CO, USA.ORCID 0000-0002-9063-0430
Dejene TufaUniversity of Colorado and Children's Hospital of Colorado, Department of Children's Cancer and Blood Disorders, Aurora, CO, USA.
Renee WoodsUniversity of Colorado and Children's Hospital of Colorado, Department of Children's Cancer and Blood Disorders, Aurora, CO, USA.
Trahan D GeorgeUniversity of Colorado and Children's Hospital of Colorado, Department of Children's Cancer and Blood Disorders, Aurora, CO, USA.
Tyler ShankUniversity of Colorado and Children's Hospital of Colorado, Department of Children's Cancer and Blood Disorders, Aurora, CO, USA.ORCID 0000-0002-1187-872X
Ashley YingstUniversity of Colorado and Children's Hospital of Colorado, Department of Children's Cancer and Blood Disorders, Aurora, CO, USA.
Jessica LakeUniversity of Colorado and Children's Hospital of Colorado, Department of Children's Cancer and Blood Disorders, Aurora, CO, USA.
Laura CobbUniversity of Colorado and Children's Hospital of Colorado, Department of Children's Cancer and Blood Disorders, Aurora, CO, USA.
Dallas JonesUniversity of Colorado and Children's Hospital of Colorado, Department of Children's Cancer and Blood Disorders, Aurora, CO, USA.
Kenneth JonesDepartment of Cell Biology, University of Oklahoma School of Medicine, Oklahoma City, OK, USA.
Michael R VernerisUniversity of Colorado and Children's Hospital of Colorado, Department of Children's Cancer and Blood Disorders, Aurora, CO, USA.
Center for Cancer and Blood Disorders · USUniversity of Oklahoma · US

Funding

University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
Lymphoid Tissue Inducer/NK22 Cells and Post-transplant Immune RecoveryR01AI100879 · NIAID · UNIVERSITY OF MINNESOTA · PI VERNERIS, MICHAEL R. · 2013 to 2017
$1.9M
NCI NIH HHS 5P30CA046934-30NCI NIH HHS P30 CA046934NIAID NIH HHS R01 AI100879NIH HHS NIH 1R01AI100879
6 · The paper itself

Abstract

Epigenetic modification is an important process during hematopoietic cell differentiation. Histone deacetylase (HDAC) inhibitors have previously been shown to enhance expansion of umbilical cord blood-derived hematopoietic stem cells (HSCs). However, the effect of HDAC inhibitors on pluripotent stem cells (PSCs) in this context is less understood. For years, investigators have considered PSC-derived natural killer (NK) and T-cell therapies. These "off-the-shelf" cellular therapies are now entering the clinic. However, the in vitro commitment of PSCs to the hematopoietic lineage is inefficient and represents a major bottleneck. We investigated whether HDAC inhibitors (HDACi) influence human PSC differentiation into CD34+CD45+ hematopoietic stem and progenitor cells (HSPCs), focusing on hemogenic endothelium (HE). Pluripotent stem cells cultured in the presence of HDACi showed a 2-5 times increase in HSPCs. Concurrent with this, HDACi-treated PSCs increased expression of 7 transcription factors (HOXA5, HOXA9, HOXA10, RUNX1, ERG, SPI1, and LCOR) recently shown to convert HE to HSPCs. ChIP-qPCR showed that SAHA upregulated acetylated-H3 at the promoter region of the above key genes. SAHA-treated human PSC-derived CD34+CD45+ cells showed primary engraftment in immunodeficient mice, but not serial transplantation. We further demonstrate that SAHA-derived HSPCs could differentiate into functional NK cells in vitro. The addition of SAHA is an easy and effective approach to overcoming the bottleneck in the transition from PSC to HSPCs for "off-the-shelf" cellular immunotherapy.

Indexed as

HemangioblastsHematopoietic Stem Cell TransplantationPluripotent Stem CellsAnimalsAntigens, CD34Cell DifferentiationCells, CulturedHistone Deacetylase InhibitorsMiceAntigens, CD34Histone Deacetylase InhibitorsCD34+CD45+HDAC inhibitorhematopoietic progenitorshemogenic endotheliumHSPCstem cells

Identifiers

PMID35349707
PMCPMC9154343
OpenAlexW4214726086

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.