Evidence map›Paper›PMID 27834190›Full record

ArticleCirculation research2017

Differentiated Smooth Muscle Cells Generate a Subpopulation of Resident Vascular Progenitor Cells in the Adventitia Regulated by Klf4.

Mark W Majesky, Henrick Horita, Allison Ostriker, Sizhao Lu, Jenna N Regan, Ashim Bagchi, Xiu Rong Dong, Joanna Poczobutt, Raphael A Nemenoff, Mary C M Weiser-Evans

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
114citing papers in PubMed, 1 pooled it
11.0field-weighted citation impact, top 1% of its field
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

114 citing papers in PubMed, 1 synthesis or guideline pooled it, 196 citations in OpenAlex.

  1. Extreme Diversity of the Human Vascular Mesenchymal Cell Landscape.Journal of the American Heart Association · 2020
    Pooled it
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  7. Phenotypic Switching of VSMCs in the Development of CVDs: Focus on miRs.International journal of molecular sciences · 2025
    Review
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  11. bioRxiv : the preprint server for biology · 2025
    Article
  12. Review
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  14. Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Multiplex Imaging for Cell Phenotyping of Early Human Atherosclerosis.Journal of the American Heart Association · 2024
    Article

54 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

Mark W MajeskyFrom the Division of Renal Diseases and Hypertension (H.H., A.O., S.L., A.B., J.P., R.A.N., M.C.M.W.-E.) and Cardiovascular Pulmonary Research Program, Division of Cardiology (R.A.N., M.C.M.W.-E.), School of Medicine, Consortium for Fibrosis Research and Translation, University of Colorado, Aurora (M.C.M.W.-E.); Division of Endocrinology, Department of Medicine, Indiana University, Indianapolis (J.N.R.); Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, WA (M.W.M., X.R.D.); and Department of Pediatrics and Department of Pathology, University of Washington, Seattle (M.W.M.). mary.weiser@ucdenver.edu mwm84@uw.edu.
Henrick HoritaFrom the Division of Renal Diseases and Hypertension (H.H., A.O., S.L., A.B., J.P., R.A.N., M.C.M.W.-E.) and Cardiovascular Pulmonary Research Program, Division of Cardiology (R.A.N., M.C.M.W.-E.), School of Medicine, Consortium for Fibrosis Research and Translation, University of Colorado, Aurora (M.C.M.W.-E.); Division of Endocrinology, Department of Medicine, Indiana University, Indianapolis (J.N.R.); Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, WA (M.W.M., X.R.D.); and Department of Pediatrics and Department of Pathology, University of Washington, Seattle (M.W.M.).
Allison OstrikerFrom the Division of Renal Diseases and Hypertension (H.H., A.O., S.L., A.B., J.P., R.A.N., M.C.M.W.-E.) and Cardiovascular Pulmonary Research Program, Division of Cardiology (R.A.N., M.C.M.W.-E.), School of Medicine, Consortium for Fibrosis Research and Translation, University of Colorado, Aurora (M.C.M.W.-E.); Division of Endocrinology, Department of Medicine, Indiana University, Indianapolis (J.N.R.); Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, WA (M.W.M., X.R.D.); and Department of Pediatrics and Department of Pathology, University of Washington, Seattle (M.W.M.).
Sizhao LuFrom the Division of Renal Diseases and Hypertension (H.H., A.O., S.L., A.B., J.P., R.A.N., M.C.M.W.-E.) and Cardiovascular Pulmonary Research Program, Division of Cardiology (R.A.N., M.C.M.W.-E.), School of Medicine, Consortium for Fibrosis Research and Translation, University of Colorado, Aurora (M.C.M.W.-E.); Division of Endocrinology, Department of Medicine, Indiana University, Indianapolis (J.N.R.); Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, WA (M.W.M., X.R.D.); and Department of Pediatrics and Department of Pathology, University of Washington, Seattle (M.W.M.).
Jenna N ReganFrom the Division of Renal Diseases and Hypertension (H.H., A.O., S.L., A.B., J.P., R.A.N., M.C.M.W.-E.) and Cardiovascular Pulmonary Research Program, Division of Cardiology (R.A.N., M.C.M.W.-E.), School of Medicine, Consortium for Fibrosis Research and Translation, University of Colorado, Aurora (M.C.M.W.-E.); Division of Endocrinology, Department of Medicine, Indiana University, Indianapolis (J.N.R.); Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, WA (M.W.M., X.R.D.); and Department of Pediatrics and Department of Pathology, University of Washington, Seattle (M.W.M.).
Ashim BagchiFrom the Division of Renal Diseases and Hypertension (H.H., A.O., S.L., A.B., J.P., R.A.N., M.C.M.W.-E.) and Cardiovascular Pulmonary Research Program, Division of Cardiology (R.A.N., M.C.M.W.-E.), School of Medicine, Consortium for Fibrosis Research and Translation, University of Colorado, Aurora (M.C.M.W.-E.); Division of Endocrinology, Department of Medicine, Indiana University, Indianapolis (J.N.R.); Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, WA (M.W.M., X.R.D.); and Department of Pediatrics and Department of Pathology, University of Washington, Seattle (M.W.M.).
Xiu Rong DongFrom the Division of Renal Diseases and Hypertension (H.H., A.O., S.L., A.B., J.P., R.A.N., M.C.M.W.-E.) and Cardiovascular Pulmonary Research Program, Division of Cardiology (R.A.N., M.C.M.W.-E.), School of Medicine, Consortium for Fibrosis Research and Translation, University of Colorado, Aurora (M.C.M.W.-E.); Division of Endocrinology, Department of Medicine, Indiana University, Indianapolis (J.N.R.); Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, WA (M.W.M., X.R.D.); and Department of Pediatrics and Department of Pathology, University of Washington, Seattle (M.W.M.).
Joanna PoczobuttFrom the Division of Renal Diseases and Hypertension (H.H., A.O., S.L., A.B., J.P., R.A.N., M.C.M.W.-E.) and Cardiovascular Pulmonary Research Program, Division of Cardiology (R.A.N., M.C.M.W.-E.), School of Medicine, Consortium for Fibrosis Research and Translation, University of Colorado, Aurora (M.C.M.W.-E.); Division of Endocrinology, Department of Medicine, Indiana University, Indianapolis (J.N.R.); Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, WA (M.W.M., X.R.D.); and Department of Pediatrics and Department of Pathology, University of Washington, Seattle (M.W.M.).
Raphael A NemenoffFrom the Division of Renal Diseases and Hypertension (H.H., A.O., S.L., A.B., J.P., R.A.N., M.C.M.W.-E.) and Cardiovascular Pulmonary Research Program, Division of Cardiology (R.A.N., M.C.M.W.-E.), School of Medicine, Consortium for Fibrosis Research and Translation, University of Colorado, Aurora (M.C.M.W.-E.); Division of Endocrinology, Department of Medicine, Indiana University, Indianapolis (J.N.R.); Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, WA (M.W.M., X.R.D.); and Department of Pediatrics and Department of Pathology, University of Washington, Seattle (M.W.M.).
Mary C M Weiser-EvansFrom the Division of Renal Diseases and Hypertension (H.H., A.O., S.L., A.B., J.P., R.A.N., M.C.M.W.-E.) and Cardiovascular Pulmonary Research Program, Division of Cardiology (R.A.N., M.C.M.W.-E.), School of Medicine, Consortium for Fibrosis Research and Translation, University of Colorado, Aurora (M.C.M.W.-E.); Division of Endocrinology, Department of Medicine, Indiana University, Indianapolis (J.N.R.); Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, WA (M.W.M., X.R.D.); and Department of Pediatrics and Department of Pathology, University of Washington, Seattle (M.W.M.). mary.weiser@ucdenver.edu mwm84@uw.edu.
Indiana University – Purdue University Indianapolis · US

Funding

University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
Colorado Clinical and Translational Sciences InstituteUL1TR001082 · NCATS · UNIVERSITY OF COLORADO DENVER · PI SOKOL, RONALD J. · 2013 to 2017
$48.0M
Reprogramming of mature smooth muscle cells to vascular progenitor cellsR01HL121877 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI MARK W. MAJESKY, Mary CM Weiser-Evans · 2015 to 2026
$7.8M
Resident Progenitor Cells in the AdventitiaR01HL123650 · NHLBI · SEATTLE CHILDREN'S HOSPITAL · PI MAJESKY, MARK W. · 2014 to 2017
$2.4M
Microenvironmental Endogenous Reprogramming of Differentiated Smooth Muscle CellsR21HL114126 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI WEISER-EVANS, MARY CM. · 2013 to 2014
$410k
NCATS NIH HHS UL1 TR001082NCI NIH HHS P30 CA046934NHLBI NIH HHS R01 HL121877NHLBI NIH HHS R01 HL123650NHLBI NIH HHS R21 HL114126
6 · The paper itself

Abstract

rationaleThe vascular adventitia is a complex layer of the vessel wall consisting of vasa vasorum microvessels, nerves, fibroblasts, immune cells, and resident progenitor cells. Adventitial progenitors express the stem cell markers, Sca1 and CD34 (adventitial sca1-positive progenitor cells [AdvSca1]), have the potential to differentiate in vitro into multiple lineages, and potentially contribute to intimal lesions in vivo.

objectiveAlthough emerging data support the existence of AdvSca1 cells, the goal of this study was to determine their origin, degree of multipotency and heterogeneity, and contribution to vessel remodeling. METHODS AND

resultsUsing 2 in vivo fate-mapping approaches combined with a smooth muscle cell (SMC) epigenetic lineage mark, we report that a subpopulation of AdvSca1 cells is generated in situ from differentiated SMCs. Our data establish that the vascular adventitia contains phenotypically distinct subpopulations of progenitor cells expressing SMC, myeloid, and hematopoietic progenitor-like properties and that differentiated SMCs are a source to varying degrees of each subpopulation. SMC-derived AdvSca1 cells exhibit a multipotent phenotype capable of differentiating in vivo into mature SMCs, resident macrophages, and endothelial-like cells. After vascular injury, SMC-derived AdvSca1 cells expand in number and are major contributors to adventitial remodeling. Induction of the transcription factor Klf4 in differentiated SMCs is essential for SMC reprogramming in vivo, whereas in vitro approaches demonstrate that Klf4 is essential for the maintenance of the AdvSca1 progenitor phenotype.

conclusionsWe propose that generation of resident vascular progenitor cells from differentiated SMCs is a normal physiological process that contributes to the vascular stem cell pool and plays important roles in arterial homeostasis and disease.

Indexed as

AdventitiaAnimalsCell DifferentiationFemaleKruppel-Like Factor 4Kruppel-Like Transcription FactorsMaleMiceMice, KnockoutMice, TransgenicMuscle, Smooth, VascularMyocytes, Smooth MusclePregnancyStem CellsKlf4 protein, mouseKruppel-Like Factor 4Kruppel-Like Transcription Factorsadventitiasmooth muscle cellsvascular remodeling

Identifiers

PMID27834190
PMCPMC5250562
OpenAlexW2557196483

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.