MSX2 suppression through inhibition of TGFβ signaling enhances hematopoietic differentiation of human embryonic stem cells

Wang, Hongtao; Wang, Mengge; Wang, Yu; Wen, Yao; Chen, Xiaoyuan; Wu, Dan; Su, Pei; Zhou, Wen; Shi, Lihong; Zhou, Jiaxi

doi:10.1186/s13287-020-01653-3

Cited by 8 publications

(2 citation statements)

References 37 publications

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“…Modulation of the TGFβ signaling pathway with the small molecule inhibitor SB431542 promotes EHT and increases hematopoietic output from HE during PSC differentiation ex vivo [97,155,165,[186][187][188][189]. However, the mode of action of SB431542 and differences in dosage or timing of its addition during in vitro differentiation have resulted in apparent contradictions (reviewed in [190]).…”

Section: Cell Signaling Regulators Of Endothelial-to-hematopoietic Tr...mentioning

confidence: 99%

De Novo Generation of Human Hematopoietic Stem Cells from Pluripotent Stem Cells for Cellular Therapy

Ding

Larochelle

2023

Cells

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The ability to manufacture human hematopoietic stem cells (HSCs) in the laboratory holds enormous promise for cellular therapy of human blood diseases. Several differentiation protocols have been developed to facilitate the emergence of HSCs from human pluripotent stem cells (PSCs). Most approaches employ a stepwise addition of cytokines and morphogens to recapitulate the natural developmental process. However, these protocols globally lack clinical relevance and uniformly induce PSCs to produce hematopoietic progenitors with embryonic features and limited engraftment and differentiation capabilities. This review examines how key intrinsic cues and extrinsic environmental inputs have been integrated within human PSC differentiation protocols to enhance the emergence of definitive hematopoiesis and how advances in genomics set the stage for imminent breakthroughs in this field.

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Section: Cell Signaling Regulators Of Endothelial-to-hematopoietic Tr...mentioning

confidence: 99%

De Novo Generation of Human Hematopoietic Stem Cells from Pluripotent Stem Cells for Cellular Therapy

Ding

Larochelle

2023

Cells

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“…MSX2 functions to maintain a balance between survival and apoptosis. Its upregulation enhances malignant phenotype [ 204 , 205 ]. It also acts as transcriptional repressor.…”

Section: Key Cardiac Transcription Factors/genesmentioning

confidence: 99%

The benign nature and rare occurrence of cardiac myxoma as a possible consequence of the limited cardiac proliferative/ regenerative potential: a systematic review

Shafi,

Siddiqui,

Jaffry

2023

BMC Cancer

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Background Cardiac Myxoma is a primary tumor of heart. Its origins, rarity of the occurrence of primary cardiac tumors and how it may be related to limited cardiac regenerative potential, are not yet entirely known. This study investigates the key cardiac genes/ transcription factors (TFs) and signaling pathways to understand these important questions. Methods Databases including PubMed, MEDLINE, and Google Scholar were searched for published articles without any date restrictions, involving cardiac myxoma, cardiac genes/TFs/signaling pathways and their roles in cardiogenesis, proliferation, differentiation, key interactions and tumorigenesis, with focus on cardiomyocytes. Results The cardiac genetic landscape is governed by a very tight control between proliferation and differentiation-related genes/TFs/pathways. Cardiac myxoma originates possibly as a consequence of dysregulations in the gene expression of differentiation regulators including Tbx5, GATA4, HAND1/2, MYOCD, HOPX, BMPs. Such dysregulations switch the expression of cardiomyocytes into progenitor-like state in cardiac myxoma development by dysregulating Isl1, Baf60 complex, Wnt, FGF, Notch, Mef2c and others. The Nkx2–5 and MSX2 contribute predominantly to both proliferation and differentiation of Cardiac Progenitor Cells (CPCs), may possibly serve roles based on the microenvironment and the direction of cell circuitry in cardiac tumorigenesis. The Nkx2–5 in cardiac myxoma may serve to limit progression of tumorigenesis as it has massive control over the proliferation of CPCs. The cardiac cell type-specific genetic programming plays governing role in controlling the tumorigenesis and regenerative potential. Conclusion The cardiomyocytes have very limited proliferative and regenerative potential. They survive for long periods of time and tightly maintain the gene expression of differentiation genes such as Tbx5, GATA4 that interact with tumor suppressors (TS) and exert TS like effect. The total effect such gene expression exerts is responsible for the rare occurrence and benign nature of primary cardiac tumors. This prevents the progression of tumorigenesis. But this also limits the regenerative and proliferative potential of cardiomyocytes. Cardiac Myxoma develops as a consequence of dysregulations in these key genes which revert the cells towards progenitor-like state, hallmark of CM. The CM development in carney complex also signifies the role of TS in cardiac cells.

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High-Efficiency Differentiation of Human Pluripotent Stem Cells to Hematopoietic Stem/Progenitor Cells in Random Positioning Machine Bioreactors

Lei

Cao

et al. 2021

Methods in Molecular Biology

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MSX2 suppression through inhibition of TGFβ signaling enhances hematopoietic differentiation of human embryonic stem cells

Cited by 8 publications

References 37 publications

De Novo Generation of Human Hematopoietic Stem Cells from Pluripotent Stem Cells for Cellular Therapy

De Novo Generation of Human Hematopoietic Stem Cells from Pluripotent Stem Cells for Cellular Therapy

The benign nature and rare occurrence of cardiac myxoma as a possible consequence of the limited cardiac proliferative/ regenerative potential: a systematic review

High-Efficiency Differentiation of Human Pluripotent Stem Cells to Hematopoietic Stem/Progenitor Cells in Random Positioning Machine Bioreactors

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