Direct chemical reprogramming of human cord blood erythroblasts to induced megakaryocytes that produce platelets

Qin, Jinhua; Zhang, Jian; Jiang, Jianan; Zhang, Bowen; Li, Jisheng; Lin, Xiaosong; Wang, Sihan; Zhu, Meiqi; Zeng, Fan; Lv, Yang; He, Liyun; Chen, Lin; Yue, Wen; Li, Yanhua; Pei, Xuetao

doi:10.1016/j.stem.2022.07.004

Cited by 15 publications

(30 citation statements)

References 85 publications

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“…According to their expression level, the cell populations can be primarily classified into three clusters. In addition, both FLI1 and KLF1 are highly expressed in the intermediate cell population suspected to be the progenitors of iMKs and EBs [96]. Namely, the pattern of expression level is concordant with the OO motif in our framework (Fig6.D).…”

Section: Section 6: the Chemical-induced Reprogramming Of Human Eryth...supporting

confidence: 77%

“…Circle size indicates the sum of in-degree and out-degree. Node colors indicate different Supermodules (adapted from [96]). Green and red edges indicate activation and inhibition, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…Of note, most of TFs filtered by noise patterns appear in the GRN constructed in the original article (8/10, 80%; Figure 6.G from [96]). As a result, we underscored that EGR3 and ETS1, which did not appear in the GRN of the original article, have been suggested to play important roles in the trans-differentiation.…”

Section: Section 6: the Chemical-induced Reprogramming Of Human Eryth...mentioning

confidence: 99%

“…Genes in cluster 5 are located in Supermodules 1 and 3, representing a decreasing tendency for expression level. Meanwhile, genes in cluster 10 are distributed in Supermodule 2 and 5, and their expression levels raise from low to high (Figure 6.D from [96]).…”

Section: Section 6: the Chemical-induced Reprogramming Of Human Eryth...mentioning

confidence: 99%

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A Logic-incorporated Gene Regulatory Network Deciphers Principles in Cell Fate Decisions

Xue

Zhang

et al. 2023

Preprint

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Organisms utilize gene regulatory networks (GRNs) to make fate decisions, but the regulatory mechanisms of transcription factors (TFs) in GRNs are exceedingly intricate. A longstanding question in this field is how these tangled interactions synergistically contribute to decision-making procedures. To comprehensively understand the role of regulatory logic in cell fate decisions, we constructed a logic-incorporated GRN model and examined its behavior under two distinct driving forces (noise-driven and signal-driven). Under the noise-driven mode, we distilled the relationship among fate bias, regulatory logic, and noise profile. Under the signal-driven mode, we bridged regulatory logic and progression-accuracy trade-off, and uncovered distinctive trajectories of reprogramming influenced by logic motifs. In differentiation, we characterized a special logic-dependent priming stage by the solution landscape. Finally, we applied our findings to decipher three biological instances: hematopoiesis, embryogenesis, and trans-differentiation. Orthogonal to the classical analysis of expression profile, we harnessed noise patterns to construct the GRN corresponding to fate transition. Our work presents a generalizable framework for top-down fate-decision studies and a practical approach to the taxonomy of cell fate decisions.

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Section: Section 6: the Chemical-induced Reprogramming Of Human Eryth...supporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: Section 6: the Chemical-induced Reprogramming Of Human Eryth...mentioning

confidence: 99%

Section: Section 6: the Chemical-induced Reprogramming Of Human Eryth...mentioning

confidence: 99%

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A Logic-incorporated Gene Regulatory Network Deciphers Principles in Cell Fate Decisions

Xue

Zhang

et al. 2023

Preprint

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“…However, the on‐demand application of platelet transfusion is often limited by the low stock availability and the short shelf life of platelets (PLTs) 2 . There exists an alternative strategy to ex vivo engineered manufacturing of induced PLTs or their precursor megakaryocytes (MKs) from stem cell differentiation or somatic cell reprogramming strategies 3,4 . Accumulated evidence indicates that stem cell‐derived MKs or PLTs can be developed as advanced therapeutic and medicinal products for patients with thrombocytopenia 4–7 …”

Section: Introductionmentioning

confidence: 99%

Baffled‐flow culture system enables the mass production of megakaryocytes from human embryonic stem cells by enhancing mitochondrial function

Zhang

Chen

et al. 2023

Cell Proliferation

Self Cite

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Human embryonic stem cells (hESCs) have become an ideal cell source for the ex vivo generation of megakaryocyte (MK) and platelet products for clinical applications. However, an ongoing challenge is to establish scalable culture systems to maximize the yield of stem cell‐derived MKs that release platelets. We defined a specific dynamic 3D manufacturing system in a baffled‐flow manner that could remarkably facilitate megakaryopoiesis and increase the yield of platelet‐producing MKs from hESCs within a 12‐day induction period. Additionally, an increased number of >16N ploidy MKs, proplatelets, and platelets were generated from induced cells harvested on Day 12 using the specific dynamic culture method. The specific dynamic culture method significantly enhanced endothelium‐to‐haematopoietic transition and early haematopoiesis. More importantly, MK fate was significantly facilitated in a specific dynamic manner during early haematopoiesis. Mechanistically, this dynamic culture significantly enhanced mitochondrial function via the oxidative phosphorylation pathway and caused differentiation skewing of hESCs toward megakaryopoiesis. This study can aid in the automatic and scalable production of MKs from stem cells using baffled‐flow bioreactors and assist in the manufacturing of hESC‐derived MK and platelet products.

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Immunological face of megakaryocytes

Li,

Chen,

Wang

2024

Front. Med.

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Direct chemical reprogramming of human cord blood erythroblasts to induced megakaryocytes that produce platelets

Cited by 15 publications

References 85 publications

A Logic-incorporated Gene Regulatory Network Deciphers Principles in Cell Fate Decisions

A Logic-incorporated Gene Regulatory Network Deciphers Principles in Cell Fate Decisions

Baffled‐flow culture system enables the mass production of megakaryocytes from human embryonic stem cells by enhancing mitochondrial function

Immunological face of megakaryocytes

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