WNT9A is a conserved regulator of hematopoietic stem and progenitor cell development

Jenna Richter, Edouard G. Stanley, Elizabeth S. Ng, Andrew G. Elefanty, David Traver, Karl Willert

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Hematopoietic stem cells (HSCs) differentiate into all cell types of the blood and can be used therapeutically to treat hematopoietic cancers and disorders. Despite decades of research, it is not yet possible to derive therapy-grade HSCs from pluripotent precursors. Analysis of HSC development in model organisms has identified some of the molecular cues that are necessary to instruct hematopoiesis in vivo, including Wnt9A, which is required during an early time window in zebrafish development. Although bona fide HSCs cannot be derived in vitro, it is possible to model human hematopoietic progenitor development by differentiating human pluripotent stem cells to hematopoietic cells. Herein, we modulate WNT9A expression during the in vitro differentiation of human embryonic stem cells to hematopoietic progenitor cells and demonstrate that WNT9A also regulates human hematopoietic progenitor cell development in vitro. Overexpression of WNT9A only impacts differentiation to CD34+/CD45+ cells during early time windows and does so in a dose-dependent manner. The cells that receive the Wnt signal—not the cells that secrete WNT9A—differentiate most efficiently to hematopoietic progenitors; this mimics the paracrine action of Wnt9a during in vivo hematopoiesis. Taken together, these data indicate that WNT9A is a conserved regulator of zebrafish and human hematopoietic development.

Original languageEnglish
Article number66
JournalGenes
Volume9
Issue number2
DOIs
Publication statusPublished - 1 Feb 2018

Keywords

  • Hematopoiesis
  • Hematopoietic stem cells
  • Human embryonic stem cells
  • Induced pluripotent stem cells
  • Wnt signaling
  • WNT9A

Cite this

Richter, Jenna ; Stanley, Edouard G. ; Ng, Elizabeth S. ; Elefanty, Andrew G. ; Traver, David ; Willert, Karl. / WNT9A is a conserved regulator of hematopoietic stem and progenitor cell development. In: Genes. 2018 ; Vol. 9, No. 2.
@article{ab694a382cb6434dbcedddb79a41f916,
title = "WNT9A is a conserved regulator of hematopoietic stem and progenitor cell development",
abstract = "Hematopoietic stem cells (HSCs) differentiate into all cell types of the blood and can be used therapeutically to treat hematopoietic cancers and disorders. Despite decades of research, it is not yet possible to derive therapy-grade HSCs from pluripotent precursors. Analysis of HSC development in model organisms has identified some of the molecular cues that are necessary to instruct hematopoiesis in vivo, including Wnt9A, which is required during an early time window in zebrafish development. Although bona fide HSCs cannot be derived in vitro, it is possible to model human hematopoietic progenitor development by differentiating human pluripotent stem cells to hematopoietic cells. Herein, we modulate WNT9A expression during the in vitro differentiation of human embryonic stem cells to hematopoietic progenitor cells and demonstrate that WNT9A also regulates human hematopoietic progenitor cell development in vitro. Overexpression of WNT9A only impacts differentiation to CD34+/CD45+ cells during early time windows and does so in a dose-dependent manner. The cells that receive the Wnt signal—not the cells that secrete WNT9A—differentiate most efficiently to hematopoietic progenitors; this mimics the paracrine action of Wnt9a during in vivo hematopoiesis. Taken together, these data indicate that WNT9A is a conserved regulator of zebrafish and human hematopoietic development.",
keywords = "Hematopoiesis, Hematopoietic stem cells, Human embryonic stem cells, Induced pluripotent stem cells, Wnt signaling, WNT9A",
author = "Jenna Richter and Stanley, {Edouard G.} and Ng, {Elizabeth S.} and Elefanty, {Andrew G.} and David Traver and Karl Willert",
year = "2018",
month = "2",
day = "1",
doi = "10.3390/genes9020066",
language = "English",
volume = "9",
journal = "Genes",
issn = "2073-4425",
publisher = "MDPI",
number = "2",

}

WNT9A is a conserved regulator of hematopoietic stem and progenitor cell development. / Richter, Jenna; Stanley, Edouard G.; Ng, Elizabeth S.; Elefanty, Andrew G.; Traver, David; Willert, Karl.

In: Genes, Vol. 9, No. 2, 66, 01.02.2018.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - WNT9A is a conserved regulator of hematopoietic stem and progenitor cell development

AU - Richter, Jenna

AU - Stanley, Edouard G.

AU - Ng, Elizabeth S.

AU - Elefanty, Andrew G.

AU - Traver, David

AU - Willert, Karl

PY - 2018/2/1

Y1 - 2018/2/1

N2 - Hematopoietic stem cells (HSCs) differentiate into all cell types of the blood and can be used therapeutically to treat hematopoietic cancers and disorders. Despite decades of research, it is not yet possible to derive therapy-grade HSCs from pluripotent precursors. Analysis of HSC development in model organisms has identified some of the molecular cues that are necessary to instruct hematopoiesis in vivo, including Wnt9A, which is required during an early time window in zebrafish development. Although bona fide HSCs cannot be derived in vitro, it is possible to model human hematopoietic progenitor development by differentiating human pluripotent stem cells to hematopoietic cells. Herein, we modulate WNT9A expression during the in vitro differentiation of human embryonic stem cells to hematopoietic progenitor cells and demonstrate that WNT9A also regulates human hematopoietic progenitor cell development in vitro. Overexpression of WNT9A only impacts differentiation to CD34+/CD45+ cells during early time windows and does so in a dose-dependent manner. The cells that receive the Wnt signal—not the cells that secrete WNT9A—differentiate most efficiently to hematopoietic progenitors; this mimics the paracrine action of Wnt9a during in vivo hematopoiesis. Taken together, these data indicate that WNT9A is a conserved regulator of zebrafish and human hematopoietic development.

AB - Hematopoietic stem cells (HSCs) differentiate into all cell types of the blood and can be used therapeutically to treat hematopoietic cancers and disorders. Despite decades of research, it is not yet possible to derive therapy-grade HSCs from pluripotent precursors. Analysis of HSC development in model organisms has identified some of the molecular cues that are necessary to instruct hematopoiesis in vivo, including Wnt9A, which is required during an early time window in zebrafish development. Although bona fide HSCs cannot be derived in vitro, it is possible to model human hematopoietic progenitor development by differentiating human pluripotent stem cells to hematopoietic cells. Herein, we modulate WNT9A expression during the in vitro differentiation of human embryonic stem cells to hematopoietic progenitor cells and demonstrate that WNT9A also regulates human hematopoietic progenitor cell development in vitro. Overexpression of WNT9A only impacts differentiation to CD34+/CD45+ cells during early time windows and does so in a dose-dependent manner. The cells that receive the Wnt signal—not the cells that secrete WNT9A—differentiate most efficiently to hematopoietic progenitors; this mimics the paracrine action of Wnt9a during in vivo hematopoiesis. Taken together, these data indicate that WNT9A is a conserved regulator of zebrafish and human hematopoietic development.

KW - Hematopoiesis

KW - Hematopoietic stem cells

KW - Human embryonic stem cells

KW - Induced pluripotent stem cells

KW - Wnt signaling

KW - WNT9A

UR - http://www.scopus.com/inward/record.url?scp=85041739254&partnerID=8YFLogxK

U2 - 10.3390/genes9020066

DO - 10.3390/genes9020066

M3 - Article

VL - 9

JO - Genes

JF - Genes

SN - 2073-4425

IS - 2

M1 - 66

ER -