Evidence map›Paper›PMID 41053000›Full record

ArticleSignal transduction and targeted therapy2025

TGF-β1-triggered maladaptive bone marrow endothelium impedes hematopoietic recovery.

Zhong-Shi Lyu, Meng-Zhu Shen, Yuan-Ya Zhang, Hui Gao, Mi Liang, Yu-Hong Chen, Zhen-Kun Wang, Xin-Yan Zhang, Dan-Dan Chen, Yuan-Yuan Zhang and 8 more

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Signal transduction and targeted therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05629260 (A Multi-center, Prospective Study of Clinical Outcome and Immune Reconstruction in G-CSF/ATG and PT-Cy Based Haploidentical Transplantation), which is not on this map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05629260 unknown statusnot on this map

A Multi-center, Prospective Study of Clinical Outcome and Immune Reconstruction in G-CSF/ATG and PT-Cy Based Haploidentical Transplantation

TypeobservationalSponsorPeking University People's HospitalRan2022 to 2025Enrolled300ConditionsHematological MalignancyArmsATG, Post-transplantation cyclophosphamide
3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. TGF-β and TNF-α Signaling Crosstalk in Human Coronary Artery Cells.International journal of molecular sciences · 2026
    Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Zhong-Shi Lyu *Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing, China.ORCID 0009-0001-5918-3003
Meng-Zhu Shen *Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing, China.
Yuan-Ya Zhang *Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
Hui GaoInstitute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
Mi LiangPeking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing, China.
Yu-Hong ChenPeking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing, China.
Zhen-Kun WangPeking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing, China.
Xin-Yan ZhangPeking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing, China.
Dan-Dan ChenPeking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing, China.
Yuan-Yuan ZhangPeking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing, China.
Meng LvPeking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing, China.
Xiao-Do MoPeking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing, China.
Lan-Ping XuPeking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing, China.ORCID 0000-0002-0267-1081
Xiao-Hui ZhangPeking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing, China.ORCID 0000-0003-0245-6792
Yu WangPeking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing, China.
Ying-Chun WangInstitute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China. ycwang@genetics.ac.cn.
Yuan KongPeking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing, China. successky@163.com.ORCID 0000-0001-5594-2642
Xiao-Jun HuangPeking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing, China. huangxiaojun@bjmu.edu.cn.ORCID 0000-0002-2145-6643

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Endothelial cells (ECs) form a critical bone marrow (BM) niche for hematopoietic stem cell regulation in homeostasis and stress states. However, BM ECs are frequently disrupted in hematologic diseases and their clinical interventions. Although transient EC injury is repairable, chronic activation of stress signals often induces maladaptive EC repair, which is a state of fibrotic reprogramming characterized by the loss of BM EC-specific functions and impaired hematopoietic-supporting ability. Although TGF-β1 (a pleiotropic cytokine) is implicated in angiogenesis and tissue repair, its role in driving BM EC maladaptation remains undefined. Here, in vitro experiments combined with a mouse model with adeno-associated virus-mediated BM EC-specific overexpression of constitutively active TGF-βRI demonstrated that TGF-β1 activation drives maladaptive BM ECs, characterized by defective vascular regeneration and impaired hematopoietic-supporting abilities. Multiomics profiling (transcriptomic and phosphoproteomic analyses) demonstrated a mechanistic link between maladaptive BM EC repair and a TGF-β1-induced secretome shift, characterized by the suppression of hematopoietic-supportive factors and the upregulation of epithelial-mesenchymal transition mediators. This effect may be driven by dysregulated vascular endothelial growth factor receptor/Notch crosstalk and subsequent p38α activation. Clinically, BM ECs from poor graft function (PGF) patients post-transplantation exhibited hyperactivated TGF-β1 signaling. In vitro experiments revealed TGF-β1 inhibition restored the function of maladaptive BM ECs from PGF patients. Subsequently, a prospective single-arm study involving luspatercept (a TGF-β ligand trap) demonstrated the significant promotion of multilineage hematopoiesis recovery in post-transplantation patients (NCT05629260). Therefore, our findings suggest that TGF-β1 may be a critical driver of BM EC maladaptation and highlight therapeutic TGF-β1 pathway inhibition for hematopoietic regeneration via BM EC remodeling.

Indexed as

Bone MarrowEndothelial CellsHematopoiesisHematopoietic Stem CellsTransforming Growth Factor beta1AnimalsEpithelial-Mesenchymal TransitionHumansMaleMiceSignal TransductionTGFB1 protein, humanTgfb1 protein, mouseTransforming Growth Factor beta1

Identifiers

PMID41053000
PMCPMC12500950

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.