Evidence map›Paper›PMID 30446598›Full record

ArticleThe EMBO journal2018

Attenuation of PKCδ enhances metabolic activity and promotes expansion of blood progenitors.

Tata Nageswara Rao, Manoj K Gupta, Samir Softic, Leo D Wang, Young C Jang, Thomas Thomou, Olivier Bezy, Rohit N Kulkarni, C Ronald Kahn, Amy J Wagers

Open access · hybridAbstract read
In one paragraph

Article in The EMBO journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.2field-weighted citation impact, top 20% 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

5 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Article
  3. Negative Regulation of the Differentiation of Flk2International journal of molecular sciences · 2020
    Article
  4. Article
  5. 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

10 authors at 2 institutions in 1 country.

Tata Nageswara RaoDepartment of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA rao.tata@unibas.ch amy_wagers@harvard.edu.ORCID 0000-0002-9928-5944
Manoj K GuptaSection on Islet Cell and Regenerative Biology, Joslin Diabetes Center, Boston, MA, USA.
Samir SofticSection on Integrative Physiology and Metabolism, Joslin Diabetes Center, Boston, MA, USA.
Leo D WangDepartment of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.
Young C JangDepartment of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.
Thomas ThomouSection on Integrative Physiology and Metabolism, Joslin Diabetes Center, Boston, MA, USA.
Olivier BezySection on Integrative Physiology and Metabolism, Joslin Diabetes Center, Boston, MA, USA.ORCID 0000-0003-4367-5043
Rohit N KulkarniSection on Islet Cell and Regenerative Biology, Joslin Diabetes Center, Boston, MA, USA.
C Ronald KahnSection on Integrative Physiology and Metabolism, Joslin Diabetes Center, Boston, MA, USA.ORCID 0000-0002-7583-9228
Amy J WagersDepartment of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA rao.tata@unibas.ch amy_wagers@harvard.edu.ORCID 0000-0002-0066-0485
Joslin Diabetes Center · USBoston Children's Hospital · US

Funding

SPECIAL ASSAY COREP30DK036836 · NIDDK · JOSLIN DIABETES CENTER · PI ROHIT N. KULKARNI · 1986 to 2026
$50.5M
Nanomedicine Center for Nucleoprotein MachinesPN2EY018244 · NEI · RICE UNIVERSITY · PI BAO, GANG · 2006 to 2015
$24.4M
Insulin Receptor Substrates and Insulin ActionR01DK033201 · NIDDK · JOSLIN DIABETES CENTER · PI KAHN, C RONALD · 1986 to 2016
$10.6M
Role of IGF-1 and Insulin Receptors Beta-Cell SurvivalR01DK067536 · NIDDK · JOSLIN DIABETES CENTER · PI ROHIT N. KULKARNI · 2004 to 2026
$8.0M
The Insulin Receptor and Its Signaling MechanismsR01DK031036 · NIDDK · JOSLIN DIABETES CENTER · PI C RONALD KAHN · 1986 to 2026
$4.2M
Role of SerpinB1 in beta cell growthR01DK103215 · NIDDK · JOSLIN DIABETES CENTER · PI KULKARNI, ROHIT N. · 2014 to 2018
$2.6M
Aging and Rejuvenation of the hematopoietic stem cell nicheDP2OD004345 · OD · JOSLIN DIABETES CENTER · PI WAGERS, AMY JO · 2008 to 2008
$2.4M
Control of HSC proliferation and migration by the transcription factor EGR1R01HL088582 · NHLBI · JOSLIN DIABETES CENTER · PI WAGERS, AMY JO · 2009 to 2013
$2.2M
In vivo gene editing of hematopoietic stem and progenitor cellsR01HL135287 · NHLBI · JOSLIN DIABETES CENTER · PI WAGERS, AMY JO · 2018 to 2021
$1.7M
NEI NIH HHS PN2 EY018244NHLBI NIH HHS R01 HL088582NHLBI NIH HHS R01 HL135287NIDDK NIH HHS P30 DK036836NIDDK NIH HHS R01 DK031036NIDDK NIH HHS R01 DK033201NIDDK NIH HHS R01 DK067536NIDDK NIH HHS R01 DK103215NIH HHS DP2 OD004345
6 · The paper itself

Abstract

A finely tuned balance of self-renewal, differentiation, proliferation, and survival governs the pool size and regenerative capacity of blood-forming hematopoietic stem and progenitor cells (HSPCs). Here, we report that protein kinase C delta (PKCδ) is a critical regulator of adult HSPC number and function that couples the proliferative and metabolic activities of HSPCs. PKCδ-deficient mice showed a pronounced increase in HSPC numbers, increased competence in reconstituting lethally irradiated recipients, enhanced long-term competitive advantage in serial transplantation studies, and an augmented HSPC recovery during stress. PKCδ-deficient HSPCs also showed accelerated proliferation and reduced apoptosis, but did not exhaust in serial transplant assays or induce leukemia. Using inducible knockout and transplantation models, we further found that PKCδ acts in a hematopoietic cell-intrinsic manner to restrict HSPC number and bone marrow regenerative function. Mechanistically, PKCδ regulates HSPC energy metabolism and coordinately governs multiple regulators within signaling pathways implicated in HSPC homeostasis. Together, these data identify PKCδ as a critical regulator of HSPC signaling and metabolism that acts to limit HSPC expansion in response to physiological and regenerative demands.

Indexed as

ApoptosisCell ProliferationSignal TransductionAnimalsBone MarrowHematopoietic Stem CellsMiceMice, KnockoutProtein Kinase C-deltaPrkcd protein, mouseProtein Kinase C-deltahematopoietic stem and progenitorsmetabolismPKCδregenerationsignaling

Identifiers

PMID30446598
PMCPMC6293338
OpenAlexW2901883599

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.