Nov/CCN3 Enhances Cord Blood Engraftment by Rapidly Recruiting Latent Human Stem Cell Activity

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved..

Umbilical cord blood (UCB) has had considerable impact in pediatric stem cell transplantation, but its wider use is limited in part by unit size. Long-term ex vivo culture offers one approach to increase engraftment capacity by seeking to expand stem and progenitor cells. Here, we show brief incubation (8 h) of UCB CD34+ cells with the matricellular regulator Nov (CCN3) increases the frequency of serially transplantable hematopoietic stem cells (HSCs) 6-fold. This rapid response suggests recruitment rather than expansion of stem cells; accordingly, in single-cell assays, Nov increases the clonogenicity of phenotypic HSCs without increasing their number through cell division. Recruitment is associated with both metabolic and transcriptional changes, and tracing of cell divisions demonstrates that the increased clonogenic activity resides within the undivided fraction of cells. Harnessing latent stem cell potential through recruitment-based approaches will inform understanding of stem cell state transitions with implications for translation to the clinic.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:26

Enthalten in:

Cell stem cell - 26(2020), 4 vom: 02. Apr., Seite 527-541.e8

Sprache:

Englisch

Beteiligte Personen:

Gupta, Rajeev [VerfasserIn]
Turati, Virginia [VerfasserIn]
Brian, Duncan [VerfasserIn]
Thrussel, Craig [VerfasserIn]
Wilbourn, Barry [VerfasserIn]
May, Gillian [VerfasserIn]
Enver, Tariq [VerfasserIn]

Links:

Volltext

Themen:

Antigens, CD34
C-MYC
HSC recruitment
Hematopoietic stem cell
Hexokinase 2
Journal Article
NOV (CCN3)
ROS
Research Support, Non-U.S. Gov't
Stem cell state transition
Umbilical cord blood transplantation

Anmerkungen:

Date Completed 27.04.2021

Date Revised 10.05.2022

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.stem.2020.02.012

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM307834239