Chemically-defined generation of human hemogenic endothelium and definitive hematopoietic progenitor cells

Yun Chang; Ramizah Syahirah; Stephanie N. Oprescu; Xuepeng Wang; Juhyung Jung; Scott H. Cooper; Sandra Torregrosa-Allen; Bennett D. Elzey; Alan Y. Hsu; Lauren N. Randolph; Yufei Sun; Shihuan Kuang; Hal E. Broxmeyer; Qing Deng; Xiaojun Lian; Xiaoping Bao

doi:10.1016/j.biomaterials.2022.121569

Chemically-defined generation of human hemogenic endothelium and definitive hematopoietic progenitor cells

Yun Chang, Ramizah Syahirah, Stephanie N. Oprescu, Xuepeng Wang, Juhyung Jung, Scott H. Cooper, Sandra Torregrosa-Allen, Bennett D. Elzey, Alan Y. Hsu, Lauren N. Randolph, Yufei Sun, Shihuan Kuang, Hal E. Broxmeyer, Qing Deng, Xiaojun Lian, Xiaoping Bao

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

13 Scopus citations

Abstract

Human hematopoietic stem cells (HSCs), which arise from aorta-gonad-mesonephros (AGM), are widely used to treat blood diseases and cancers. However, a technique for their robust generation in vitro is still missing. Here we show temporal manipulation of Wnt signaling is sufficient and essential to induce AGM-like hematopoiesis from human pluripotent stem cells. TGFβ inhibition at the stage of aorta-like SOX17⁺CD235a⁻ hemogenic endothelium yielded AGM-like hematopoietic progenitors, which closely resembled primary cord blood HSCs at the transcriptional level and contained diverse lineage-primed progenitor populations via single cell RNA-sequencing analysis. Notably, the resulting definitive cells presented lymphoid and myeloid potential in vitro; and could home to a definitive hematopoietic site in zebrafish and rescue bloodless zebrafish after transplantation. Engraftment and multilineage repopulating activities were also observed in mouse recipients. Together, our work provided a chemically-defined and feeder-free culture platform for scalable generation of AGM-like hematopoietic progenitor cells, leading to enhanced production of functional blood and immune cells for various therapeutic applications.

Original language	English (US)
Article number	121569
Journal	Biomaterials
Volume	285
DOIs	https://doi.org/10.1016/j.biomaterials.2022.121569
State	Published - Jun 2022

All Science Journal Classification (ASJC) codes

Biophysics
Bioengineering
Ceramics and Composites
Biomaterials
Mechanics of Materials

UN SDGs

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

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10.1016/j.biomaterials.2022.121569

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Chang, Y., Syahirah, R., Oprescu, S. N., Wang, X., Jung, J., Cooper, S. H., Torregrosa-Allen, S., Elzey, B. D., Hsu, A. Y., Randolph, L. N., Sun, Y., Kuang, S., Broxmeyer, H. E., Deng, Q., Lian, X., & Bao, X. (2022). Chemically-defined generation of human hemogenic endothelium and definitive hematopoietic progenitor cells. Biomaterials, 285, Article 121569. https://doi.org/10.1016/j.biomaterials.2022.121569

@article{69a0efe031ea4aa0a5c497b3d956cacb,

title = "Chemically-defined generation of human hemogenic endothelium and definitive hematopoietic progenitor cells",

abstract = "Human hematopoietic stem cells (HSCs), which arise from aorta-gonad-mesonephros (AGM), are widely used to treat blood diseases and cancers. However, a technique for their robust generation in vitro is still missing. Here we show temporal manipulation of Wnt signaling is sufficient and essential to induce AGM-like hematopoiesis from human pluripotent stem cells. TGFβ inhibition at the stage of aorta-like SOX17+CD235a− hemogenic endothelium yielded AGM-like hematopoietic progenitors, which closely resembled primary cord blood HSCs at the transcriptional level and contained diverse lineage-primed progenitor populations via single cell RNA-sequencing analysis. Notably, the resulting definitive cells presented lymphoid and myeloid potential in vitro; and could home to a definitive hematopoietic site in zebrafish and rescue bloodless zebrafish after transplantation. Engraftment and multilineage repopulating activities were also observed in mouse recipients. Together, our work provided a chemically-defined and feeder-free culture platform for scalable generation of AGM-like hematopoietic progenitor cells, leading to enhanced production of functional blood and immune cells for various therapeutic applications.",

author = "Yun Chang and Ramizah Syahirah and Oprescu, {Stephanie N.} and Xuepeng Wang and Juhyung Jung and Cooper, {Scott H.} and Sandra Torregrosa-Allen and Elzey, {Bennett D.} and Hsu, {Alan Y.} and Randolph, {Lauren N.} and Yufei Sun and Shihuan Kuang and Broxmeyer, {Hal E.} and Qing Deng and Xiaojun Lian and Xiaoping Bao",

note = "Publisher Copyright: {\textcopyright} 2022",

year = "2022",

month = jun,

doi = "10.1016/j.biomaterials.2022.121569",

language = "English (US)",

volume = "285",

journal = "Biomaterials",

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Chang, Y, Syahirah, R, Oprescu, SN, Wang, X, Jung, J, Cooper, SH, Torregrosa-Allen, S, Elzey, BD, Hsu, AY, Randolph, LN, Sun, Y, Kuang, S, Broxmeyer, HE, Deng, Q, Lian, X & Bao, X 2022, 'Chemically-defined generation of human hemogenic endothelium and definitive hematopoietic progenitor cells', Biomaterials, vol. 285, 121569. https://doi.org/10.1016/j.biomaterials.2022.121569

TY - JOUR

T1 - Chemically-defined generation of human hemogenic endothelium and definitive hematopoietic progenitor cells

AU - Chang, Yun

AU - Syahirah, Ramizah

AU - Oprescu, Stephanie N.

AU - Wang, Xuepeng

AU - Jung, Juhyung

AU - Cooper, Scott H.

AU - Torregrosa-Allen, Sandra

AU - Elzey, Bennett D.

AU - Hsu, Alan Y.

AU - Randolph, Lauren N.

AU - Sun, Yufei

AU - Kuang, Shihuan

AU - Broxmeyer, Hal E.

AU - Deng, Qing

AU - Lian, Xiaojun

AU - Bao, Xiaoping

PY - 2022/6

Y1 - 2022/6

N2 - Human hematopoietic stem cells (HSCs), which arise from aorta-gonad-mesonephros (AGM), are widely used to treat blood diseases and cancers. However, a technique for their robust generation in vitro is still missing. Here we show temporal manipulation of Wnt signaling is sufficient and essential to induce AGM-like hematopoiesis from human pluripotent stem cells. TGFβ inhibition at the stage of aorta-like SOX17+CD235a− hemogenic endothelium yielded AGM-like hematopoietic progenitors, which closely resembled primary cord blood HSCs at the transcriptional level and contained diverse lineage-primed progenitor populations via single cell RNA-sequencing analysis. Notably, the resulting definitive cells presented lymphoid and myeloid potential in vitro; and could home to a definitive hematopoietic site in zebrafish and rescue bloodless zebrafish after transplantation. Engraftment and multilineage repopulating activities were also observed in mouse recipients. Together, our work provided a chemically-defined and feeder-free culture platform for scalable generation of AGM-like hematopoietic progenitor cells, leading to enhanced production of functional blood and immune cells for various therapeutic applications.

AB - Human hematopoietic stem cells (HSCs), which arise from aorta-gonad-mesonephros (AGM), are widely used to treat blood diseases and cancers. However, a technique for their robust generation in vitro is still missing. Here we show temporal manipulation of Wnt signaling is sufficient and essential to induce AGM-like hematopoiesis from human pluripotent stem cells. TGFβ inhibition at the stage of aorta-like SOX17+CD235a− hemogenic endothelium yielded AGM-like hematopoietic progenitors, which closely resembled primary cord blood HSCs at the transcriptional level and contained diverse lineage-primed progenitor populations via single cell RNA-sequencing analysis. Notably, the resulting definitive cells presented lymphoid and myeloid potential in vitro; and could home to a definitive hematopoietic site in zebrafish and rescue bloodless zebrafish after transplantation. Engraftment and multilineage repopulating activities were also observed in mouse recipients. Together, our work provided a chemically-defined and feeder-free culture platform for scalable generation of AGM-like hematopoietic progenitor cells, leading to enhanced production of functional blood and immune cells for various therapeutic applications.

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Chemically-defined generation of human hemogenic endothelium and definitive hematopoietic progenitor cells

Abstract

All Science Journal Classification (ASJC) codes

UN SDGs

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