Evidence map›Paper›PMID 36945732›Full record

ArticleStem cells (Dayton, Ohio)2023

Dynamics of Chromatin Accessibility During Hematopoietic Stem Cell Differentiation Into Progressively Lineage-Committed Progeny.

Eric W Martin, Alessandra Rodriguez Y Baena, Roman E Reggiardo, Atesh K Worthington, Connor S Mattingly, Donna M Poscablo, Jana Krietsch, Michael T McManus, Susan Carpenter, Daniel H Kim and 1 more

Abstract read
In one paragraph

Article in Stem cells (Dayton, Ohio), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing 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.

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

17 citing papers in PubMed.

  1. Predictive control of human pancreatic cell fate using a digital model ofbioRxiv : the preprint server for biology · 2026
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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

11 authors.

Eric W MartinInstitute for the Biology of Stem Cells, Department of Molecular, Cell and Developmental Biology, University of California Santa Cruz, Santa Cruz, CA, USA.
Alessandra Rodriguez Y BaenaInstitute for the Biology of Stem Cells, Department of Molecular, Cell and Developmental Biology, University of California Santa Cruz, Santa Cruz, CA, USA.
Roman E ReggiardoInstitute for the Biology of Stem Cells, Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, CA, USA.
Atesh K WorthingtonInstitute for the Biology of Stem Cells, Department of Molecular, Cell and Developmental Biology, University of California Santa Cruz, Santa Cruz, CA, USA.
Connor S MattinglyInstitute for the Biology of Stem Cells, Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, CA, USA.
Donna M PoscabloInstitute for the Biology of Stem Cells, Department of Molecular, Cell and Developmental Biology, University of California Santa Cruz, Santa Cruz, CA, USA.
Jana KrietschInstitute for the Biology of Stem Cells, Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, CA, USA.
Michael T McManusDepartment of Microbiology and Immunology, Diabetes Center, W.M. Keck Center for Noncoding RNAs, University of California San Francisco, San Francisco, CA, USA.
Susan CarpenterInstitute for the Biology of Stem Cells, Department of Molecular, Cell and Developmental Biology, University of California Santa Cruz, Santa Cruz, CA, USA.
Daniel H KimInstitute for the Biology of Stem Cells, Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, CA, USA.
E Camilla ForsbergInstitute for the Biology of Stem Cells, Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, CA, USA.ORCID 0000-0002-8740-4299

Funding

UNIVERSITY OF CALIFORNIA, SANTA CRUZ IMSD PROGRAMR25GM058903 · NIGMS · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI JURICA, MELISSA S · 1999 to 2019
$12.2M
Defining the cause and consequence of aging-specific platelet specification from hematopoietic stem cellsR01AG062879 · NIA · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI CAMILLA FORSBERG · 2019 to 2026
$4.9M
Role and Regulation of a Novel, Developmentally Restricted Hematopoietic Stem CellR01DK100917 · NIDDK · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI FORSBERG, CAMILLA · 2013 to 2024
$3.9M
Training Program/Molecular/Cell/Developmental BiologyT32GM008646 · NIGMS · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI STROME, SUSAN · 1999 to 2018
$3.7M
Regulation of Chromatin Structure Dynamics in Hematopoietic and Leukemic Stem CelR01HL115158 · NHLBI · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI FORSBERG, CAMILLA · 2013 to 2017
$2.1M
UC Santa Cruz Training Program In Genomic SciencesT32HG008345 · NHGRI · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI BROOKS, ANGELA NORIE, GREEN, RICHARD EDWARD · 2015 to 2020
$1.4M
Defining regulators of hematopoietic stem cell self-renewal and lineage potentialF31HL151199 · NHLBI · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI WORTHINGTON, ATESH K · 2020 to 2022
$115k
Cell free RNA liquid biopsiesF99DK131504 · NIDDK · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI REGGIARDO, ROMAN E · 2021 to 2022
$88k
Chromatin Accessibility and Nuclear Localization Effects on Hematopoietic Lineage FateF31HL144115 · NHLBI · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI MARTIN, ERIC W · 2019 to 2020
$75k
NHGRI NIH HHS T32 HG008345NHLBI NIH HHS F31 HL144115NHLBI NIH HHS F31 HL151199NHLBI NIH HHS R01 HL115158NIA NIH HHS R01 AG062879NIDDK NIH HHS F99 DK131504NIDDK NIH HHS R01 DK100917NIGMS NIH HHS R25 GM058903NIGMS NIH HHS T32 GM008646
6 · The paper itself

Abstract

Epigenetic mechanisms regulate the multilineage differentiation capacity of hematopoietic stem cells (HSCs) into a variety of blood and immune cells. Mapping the chromatin dynamics of functionally defined cell populations will shed mechanistic insight into 2 major, unanswered questions in stem cell biology: how does epigenetic identity contribute to a cell type's lineage potential, and how do cascades of chromatin remodeling dictate ensuing fate decisions? Our recent work revealed evidence of multilineage gene priming in HSCs, where open cis-regulatory elements (CREs) exclusively shared between HSCs and unipotent lineage cells were enriched for DNA binding motifs of known lineage-specific transcription factors. Oligopotent progenitor populations operating between the HSCs and unipotent cells play essential roles in effecting hematopoietic homeostasis. To test the hypothesis that selective HSC-primed lineage-specific CREs remain accessible throughout differentiation, we used ATAC-seq to map the temporal dynamics of chromatin remodeling during progenitor differentiation. We observed epigenetic-driven clustering of oligopotent and unipotent progenitors into distinct erythromyeloid and lymphoid branches, with multipotent HSCs and MPPs associating with the erythromyeloid lineage. We mapped the dynamics of lineage-primed CREs throughout hematopoiesis and identified both unique and shared CREs as potential lineage reinforcement mechanisms at fate branch points. Additionally, quantification of genome-wide peak count and size revealed overall greater chromatin accessibility in HSCs, allowing us to identify HSC-unique peaks as putative regulators of self-renewal and multilineage potential. Finally, CRISPRi-mediated targeting of ATACseq-identified putative CREs in HSCs allowed us to demonstrate the functional role of selective CREs in lineage-specific gene expression. These findings provide insight into the regulation of stem cell multipotency and lineage commitment throughout hematopoiesis and serve as a resource to test functional drivers of hematopoietic lineage fate.

Indexed as

ChromatinHematopoiesisCell DifferentiationCell LineageHematopoietic Stem CellsChromatincell fate decisionschromatin accessibilityepigeneticshematopoiesishematopoietic stem and progenitor cells

Identifiers

PMID36945732
PMCPMC10183972

What OpenQuestion holds

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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.