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

doi:10.3390/genes9020066

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

Administration (CBS)

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

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 language	English (US)
Article number	66
Journal	Genes
Volume	9
Issue number	2
DOIs	https://doi.org/10.3390/genes9020066
State	Published - Feb 2018

Bibliographical note

Funding Information:
Acknowledgments: This work was supported in part by the NIH/NHLBI under the Grant R01HL135205 and was made possible in part by the CIRM Major Facilities grant (FA1-00607) to the Sanford Consortium for Regenerative Medicine. JR was supported in part by the UCSD Interdisciplinary Stem Cell Training Program (CIRM TG2-01154) and by the American Heart Association Predoctoral Fellowship 16PRE27340012. E.G.S. and A.G.E. are Research Fellows of the NHMRC of Australia.

Publisher Copyright:
© 2018 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access

10.3390/genes9020066

OpenUrl availability

Full text

Cite this

@article{cf56c6a1a96f49d7923587d8ae038d92,

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, WNT9A, Wnt signaling",

author = "Jenna Richter and Stanley, {Edouard G.} and Ng, {Elizabeth S.} and Elefanty, {Andrew G.} and David Traver and Karl Willert",

note = "Funding Information: Acknowledgments: This work was supported in part by the NIH/NHLBI under the Grant R01HL135205 and was made possible in part by the CIRM Major Facilities grant (FA1-00607) to the Sanford Consortium for Regenerative Medicine. JR was supported in part by the UCSD Interdisciplinary Stem Cell Training Program (CIRM TG2-01154) and by the American Heart Association Predoctoral Fellowship 16PRE27340012. E.G.S. and A.G.E. are Research Fellows of the NHMRC of Australia. Publisher Copyright: {\textcopyright} 2018 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2018",

month = feb,

doi = "10.3390/genes9020066",

language = "English (US)",

volume = "9",

journal = "Genes",

issn = "2073-4425",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "2",

}

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

N1 - Funding Information: Acknowledgments: This work was supported in part by the NIH/NHLBI under the Grant R01HL135205 and was made possible in part by the CIRM Major Facilities grant (FA1-00607) to the Sanford Consortium for Regenerative Medicine. JR was supported in part by the UCSD Interdisciplinary Stem Cell Training Program (CIRM TG2-01154) and by the American Heart Association Predoctoral Fellowship 16PRE27340012. E.G.S. and A.G.E. are Research Fellows of the NHMRC of Australia. Publisher Copyright: © 2018 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2018/2

Y1 - 2018/2

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 - WNT9A

KW - Wnt signaling

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

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

U2 - 10.3390/genes9020066

DO - 10.3390/genes9020066

M3 - Article

C2 - 29382179

AN - SCOPUS:85041739254

SN - 2073-4425

VL - 9

JO - Genes

JF - Genes

IS - 2

M1 - 66

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

Access

OpenUrl availability

Other files and links

Fingerprint

Cite this