Chromatin and Transcriptional Analysis of Mesoderm Progenitor Cells Identifies HOPX as a Regulator of Primitive Hematopoiesis
We analyzed chromatin dynamics and transcriptional activity of human embryonic stem cell (hESC)-derived cardiac progenitor cells (CPCs) and KDR+/CD34+ endothelial cells generated from different mesodermal origins. Using an unbiased algorithm to hierarchically rank genes modulated at the level of chr...
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doaj-e989b68c8d95474a80bdd72eab2acc562020-11-25T01:46:35ZengElsevierCell Reports2211-12472017-08-012071597160810.1016/j.celrep.2017.07.067Chromatin and Transcriptional Analysis of Mesoderm Progenitor Cells Identifies HOPX as a Regulator of Primitive HematopoiesisNathan J. Palpant0Yuliang Wang1Brandon Hadland2Rebecca J. Zaunbrecher3Meredith Redd4Daniel Jones5Lil Pabon6Rajan Jain7Jonathan Epstein8Walter L. Ruzzo9Ying Zheng10Irwin Bernstein11Adam Margolin12Charles E. Murry13Department of Pathology, University of Washington School of Medicine, Seattle, WA 98109, USADepartment of Computer Science, University of Washington School of Medicine, Seattle, WA 98109, USAClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USADepartment of Bioengineering, University of Washington School of Medicine, Seattle, WA 98109, USADepartment of Bioengineering, University of Washington School of Medicine, Seattle, WA 98109, USADepartment of Computer Science, University of Washington School of Medicine, Seattle, WA 98109, USADepartment of Pathology, University of Washington School of Medicine, Seattle, WA 98109, USADepartment of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Computer Science, University of Washington School of Medicine, Seattle, WA 98109, USADepartment of Bioengineering, University of Washington School of Medicine, Seattle, WA 98109, USAClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USADepartment of Biomedical Engineering, Oregon Health & Science University, Portland, OR 97239, USADepartment of Pathology, University of Washington School of Medicine, Seattle, WA 98109, USAWe analyzed chromatin dynamics and transcriptional activity of human embryonic stem cell (hESC)-derived cardiac progenitor cells (CPCs) and KDR+/CD34+ endothelial cells generated from different mesodermal origins. Using an unbiased algorithm to hierarchically rank genes modulated at the level of chromatin and transcription, we identified candidate regulators of mesodermal lineage determination. HOPX, a non-DNA-binding homeodomain protein, was identified as a candidate regulator of blood-forming endothelial cells. Using HOPX reporter and knockout hESCs, we show that HOPX regulates blood formation. Loss of HOPX does not impact endothelial fate specification but markedly reduces primitive hematopoiesis, acting at least in part through failure to suppress Wnt/β-catenin signaling. Thus, chromatin state analysis permits identification of regulators of mesodermal specification, including a conserved role for HOPX in governing primitive hematopoiesis.http://www.sciencedirect.com/science/article/pii/S2211124717310604human pluripotent stem cellcardiovascularhematopoiesischromatin dynamicsdifferentiationgenome engineeringWnt signalingepigeneticscardiac |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nathan J. Palpant Yuliang Wang Brandon Hadland Rebecca J. Zaunbrecher Meredith Redd Daniel Jones Lil Pabon Rajan Jain Jonathan Epstein Walter L. Ruzzo Ying Zheng Irwin Bernstein Adam Margolin Charles E. Murry |
spellingShingle |
Nathan J. Palpant Yuliang Wang Brandon Hadland Rebecca J. Zaunbrecher Meredith Redd Daniel Jones Lil Pabon Rajan Jain Jonathan Epstein Walter L. Ruzzo Ying Zheng Irwin Bernstein Adam Margolin Charles E. Murry Chromatin and Transcriptional Analysis of Mesoderm Progenitor Cells Identifies HOPX as a Regulator of Primitive Hematopoiesis Cell Reports human pluripotent stem cell cardiovascular hematopoiesis chromatin dynamics differentiation genome engineering Wnt signaling epigenetics cardiac |
author_facet |
Nathan J. Palpant Yuliang Wang Brandon Hadland Rebecca J. Zaunbrecher Meredith Redd Daniel Jones Lil Pabon Rajan Jain Jonathan Epstein Walter L. Ruzzo Ying Zheng Irwin Bernstein Adam Margolin Charles E. Murry |
author_sort |
Nathan J. Palpant |
title |
Chromatin and Transcriptional Analysis of Mesoderm Progenitor Cells Identifies HOPX as a Regulator of Primitive Hematopoiesis |
title_short |
Chromatin and Transcriptional Analysis of Mesoderm Progenitor Cells Identifies HOPX as a Regulator of Primitive Hematopoiesis |
title_full |
Chromatin and Transcriptional Analysis of Mesoderm Progenitor Cells Identifies HOPX as a Regulator of Primitive Hematopoiesis |
title_fullStr |
Chromatin and Transcriptional Analysis of Mesoderm Progenitor Cells Identifies HOPX as a Regulator of Primitive Hematopoiesis |
title_full_unstemmed |
Chromatin and Transcriptional Analysis of Mesoderm Progenitor Cells Identifies HOPX as a Regulator of Primitive Hematopoiesis |
title_sort |
chromatin and transcriptional analysis of mesoderm progenitor cells identifies hopx as a regulator of primitive hematopoiesis |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2017-08-01 |
description |
We analyzed chromatin dynamics and transcriptional activity of human embryonic stem cell (hESC)-derived cardiac progenitor cells (CPCs) and KDR+/CD34+ endothelial cells generated from different mesodermal origins. Using an unbiased algorithm to hierarchically rank genes modulated at the level of chromatin and transcription, we identified candidate regulators of mesodermal lineage determination. HOPX, a non-DNA-binding homeodomain protein, was identified as a candidate regulator of blood-forming endothelial cells. Using HOPX reporter and knockout hESCs, we show that HOPX regulates blood formation. Loss of HOPX does not impact endothelial fate specification but markedly reduces primitive hematopoiesis, acting at least in part through failure to suppress Wnt/β-catenin signaling. Thus, chromatin state analysis permits identification of regulators of mesodermal specification, including a conserved role for HOPX in governing primitive hematopoiesis. |
topic |
human pluripotent stem cell cardiovascular hematopoiesis chromatin dynamics differentiation genome engineering Wnt signaling epigenetics cardiac |
url |
http://www.sciencedirect.com/science/article/pii/S2211124717310604 |
work_keys_str_mv |
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