Lineage-tracing hematopoietic stem cell origins in vivo to efficiently make human HLF plus HOXA plus hematopoietic from pluripotent stem cells

被引：12

作者：

Fowler, Jonas L. ^{[1
,2
,11
]}

Zheng, Sherry Li ^{[1
,2
]}

Nguyen, Alana ^{[1
,2
,12
]}

Chen, Angela ^{[1
,2
,3
,13
]}

Xiong, Xiaochen ^{[1
,2
,14
]}

Chai, Timothy ^{[1
,2
]}

Chen, Julie Y. ^{[1
,2
]}

Karigane, Daiki ^{[1
,3
]}

Banuelos, Allison M. ^{[1
,4
]}

Niizuma, Kouta ^{[1
,5
]}

Kayamori, Kensuke ^{[1
,3
]}

Nishimura, Toshinobu ^{[1
,5
,15
]}

Cromer, M. Kyle ^{[6
]}

Gonzalez-Perez, David ^{[7
]}

Mason, Charlotte ^{[7
]}

Liu, Daniel Dan ^{[1
,4
]}

Yilmaz, Leyla ^{[1
,4
]}

Miquerol, Lucile ^{[8
]}

Porteus, Matthew H. ^{[1
,9
]}

Luca, Vincent C. ^{[7
]}

Majeti, Ravindra ^{[1
,3
]}

Nakauchi, Hiromitsu ^{[1
]}

Red-Horse, Kristy ^{[1
,10
]}

Weissman, Irving L. ^{[1
,4
]}

Ang, Lay Teng ^{[1
]}

Loh, Kyle M. ^{[1
,2
]}

机构：

[1] Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA

[2] Stanford Univ, Dept Dev Biol, Stanford, CA 94305 USA

[3] Stanford Univ, Dept Med, Div Hematol, Stanford, CA 94305 USA

[4] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA

[5] Stanford Univ, Dept Genet, Stanford, CA 94305 USA

[6] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA

[7] H Lee Moffitt Canc Ctr & Res Inst, Dept Drug Discovery, Tampa, FL 33612 USA

[8] Aix Marseille Univ, IBDM, CNRS UMR 7288, F-13288 Marseille, France

[9] Stanford Univ, Dept Pediat, Stanford, CA 94305 USA

[10] Stanford Univ, Howard Hughes Med Inst, Dept Biol, Stanford, CA 94305 USA

[11] Walking Fish Therapeut, South San Francisco, CA USA

[12] Univ Calif Davis, Sch Vet Med, Davis, CA 95616 USA

[13] Orca Bio, Menlo Pk, CA 94025 USA

[14] Stanford Univ, Dept Biol, Stanford, CA 94305 USA

[15] Century Therapeut, Philadelphia, PA 19104 USA

来源：

DEVELOPMENTAL CELL | 2024年 / 59卷 / 09期

关键词：

DEFINITIVE HEMATOPOIESIS; HAEMOGENIC ENDOTHELIUM; PROGENITOR CELLS; CLONAL ANALYSIS; YOLK-SAC; HEMOGENIC ENDOTHELIUM; AORTIC ENDOTHELIUM; MESODERM FORMATION; PRIMITIVE STREAK; RETINOIC ACID;

D O I：

10.1016/j.devcel.2024.03.003

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The developmental origin of blood -forming hematopoietic stem cells (HSCs) is a longstanding question. Here, our non-invasive genetic lineage tracing in mouse embryos pinpoints that artery endothelial generate HSCs. Arteries are transiently competent to generate HSCs for 2.5 days (similar to E8.5-E11) but subsequently cease, delimiting a narrow time frame for HSC formation in vivo . Guided by the arterial origins blood, we efficiently and rapidly differentiate human pluripotent stem cells (hPSCs) into posterior primitive streak, lateral mesoderm, artery endothelium, hemogenic endothelium, and >90% pure hematopoietic genitors within 10 days. hPSC-derived hematopoietic progenitors generate T, B, NK, erythroid, and myeloid cells in vitro and, critically, express hallmark HSC transcription factors HLF and HOXA5-HOXA10 , which previously challenging to upregulate. We differentiated hPSCs into highly enriched HLF + HOXA + hematopoietic progenitors with near-stoichiometric efficiency by blocking formation of unwanted lineages at each ferentiation step. hPSC-derived HLF + HOXA + hematopoietic progenitors could avail both basic research cellular therapies.

引用

页码：1110 / 1131.e22

页数：45

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