Imaging Hematopoietic Precursor Division in Real Time

Mingfu Wu; Hyog Young Kwon; Frederique Rattis; Jordan Blum; Chen Zhao; Rina Ashkenazi; Trachette L L. Jackson; Nicholas Gaiano; Tim Oliver; Tannishtha Reya

doi:10.1016/j.stem.2007.08.009

Imaging Hematopoietic Precursor Division in Real Time

Mingfu Wu, Hyog Young Kwon, Frederique Rattis, Jordan Blum, Chen Zhao, Rina Ashkenazi, Trachette L L. Jackson, Nicholas Gaiano, Tim Oliver, Tannishtha Reya

Mathematics

Research output: Contribution to journal › Article › peer-review

237 Scopus citations

Abstract

Stem cells are thought to balance self-renewal and differentiation through asymmetric and symmetric divisions, but whether such divisions occur during hematopoietic development remains unknown. Using a Notch reporter mouse, in which GFP acts as a sensor for differentiation, we image hematopoietic precursors and show that they undergo both symmetric and asymmetric divisions. In addition we show that the balance between these divisions is not hardwired but responsive to extrinsic and intrinsic cues. Precursors in a prodifferentiation environment preferentially divide asymmetrically, whereas those in a prorenewal environment primarily divide symmetrically. Oncoproteins can also influence division pattern: although BCR-ABL predominantly alters the rate of division and death, NUP98-HOXA9 promotes symmetric division, suggesting that distinct oncogenes subvert different aspects of cellular function. These studies establish a system for tracking division of hematopoietic precursors and show that the balance of symmetric and asymmetric division can be influenced by the microenvironment and subverted by oncogenes.

Original language	English (US)
Pages (from-to)	541-554
Number of pages	14
Journal	Cell Stem Cell
Volume	1
Issue number	5
DOIs	https://doi.org/10.1016/j.stem.2007.08.009
State	Published - Nov 15 2007

Bibliographical note

Funding Information:
We are grateful to Brigid Hogan for invaluable help and advice, Mike Dustin for advice on time-lapse microscopy, Gary Gilliland and Craig Jordan for providing the NUP98-HOXA9 construct, Ann Marie Pendergast and Warren Pear for providing the BCR-ABL construct, Motonari Kondo for providing Rag2 −/− IL2rγ −/− mice, Alan Chen and Yin Yiu for excellent technical help, Mike Cook and Beth Harvat for cell sorting, and Anthony Means, Brigid Hogan, and Terry Lechler for critical review of the manuscript. T.R. is a recipient of a Cancer Research Institute Investigator Award, an Ellison Medical Foundation New Scholar award, and a Leukemia and Lymphoma Society Scholar Award. This work was also supported by NIH grants DK63031 and DK072234 and a Duke Stem Cell Research Program grant to T.R.

Keywords

STEMCELL

Access

10.1016/j.stem.2007.08.009

OpenUrl availability

Full text

Cite this

@article{4f9ae03b5c6d4144939923aaa429b664,

title = "Imaging Hematopoietic Precursor Division in Real Time",

abstract = "Stem cells are thought to balance self-renewal and differentiation through asymmetric and symmetric divisions, but whether such divisions occur during hematopoietic development remains unknown. Using a Notch reporter mouse, in which GFP acts as a sensor for differentiation, we image hematopoietic precursors and show that they undergo both symmetric and asymmetric divisions. In addition we show that the balance between these divisions is not hardwired but responsive to extrinsic and intrinsic cues. Precursors in a prodifferentiation environment preferentially divide asymmetrically, whereas those in a prorenewal environment primarily divide symmetrically. Oncoproteins can also influence division pattern: although BCR-ABL predominantly alters the rate of division and death, NUP98-HOXA9 promotes symmetric division, suggesting that distinct oncogenes subvert different aspects of cellular function. These studies establish a system for tracking division of hematopoietic precursors and show that the balance of symmetric and asymmetric division can be influenced by the microenvironment and subverted by oncogenes.",

keywords = "STEMCELL",

author = "Mingfu Wu and Kwon, {Hyog Young} and Frederique Rattis and Jordan Blum and Chen Zhao and Rina Ashkenazi and Jackson, {Trachette L L.} and Nicholas Gaiano and Tim Oliver and Tannishtha Reya",

note = "Funding Information: We are grateful to Brigid Hogan for invaluable help and advice, Mike Dustin for advice on time-lapse microscopy, Gary Gilliland and Craig Jordan for providing the NUP98-HOXA9 construct, Ann Marie Pendergast and Warren Pear for providing the BCR-ABL construct, Motonari Kondo for providing Rag2 −/− IL2rγ −/− mice, Alan Chen and Yin Yiu for excellent technical help, Mike Cook and Beth Harvat for cell sorting, and Anthony Means, Brigid Hogan, and Terry Lechler for critical review of the manuscript. T.R. is a recipient of a Cancer Research Institute Investigator Award, an Ellison Medical Foundation New Scholar award, and a Leukemia and Lymphoma Society Scholar Award. This work was also supported by NIH grants DK63031 and DK072234 and a Duke Stem Cell Research Program grant to T.R. ",

year = "2007",

month = nov,

day = "15",

doi = "10.1016/j.stem.2007.08.009",

language = "English (US)",

volume = "1",

pages = "541--554",

journal = "Cell Stem Cell",

issn = "1934-5909",

publisher = "Cell Press",

number = "5",

}

TY - JOUR

T1 - Imaging Hematopoietic Precursor Division in Real Time

AU - Wu, Mingfu

AU - Kwon, Hyog Young

AU - Rattis, Frederique

AU - Blum, Jordan

AU - Zhao, Chen

AU - Ashkenazi, Rina

AU - Jackson, Trachette L L.

AU - Gaiano, Nicholas

AU - Oliver, Tim

AU - Reya, Tannishtha

N1 - Funding Information: We are grateful to Brigid Hogan for invaluable help and advice, Mike Dustin for advice on time-lapse microscopy, Gary Gilliland and Craig Jordan for providing the NUP98-HOXA9 construct, Ann Marie Pendergast and Warren Pear for providing the BCR-ABL construct, Motonari Kondo for providing Rag2 −/− IL2rγ −/− mice, Alan Chen and Yin Yiu for excellent technical help, Mike Cook and Beth Harvat for cell sorting, and Anthony Means, Brigid Hogan, and Terry Lechler for critical review of the manuscript. T.R. is a recipient of a Cancer Research Institute Investigator Award, an Ellison Medical Foundation New Scholar award, and a Leukemia and Lymphoma Society Scholar Award. This work was also supported by NIH grants DK63031 and DK072234 and a Duke Stem Cell Research Program grant to T.R.

PY - 2007/11/15

Y1 - 2007/11/15

N2 - Stem cells are thought to balance self-renewal and differentiation through asymmetric and symmetric divisions, but whether such divisions occur during hematopoietic development remains unknown. Using a Notch reporter mouse, in which GFP acts as a sensor for differentiation, we image hematopoietic precursors and show that they undergo both symmetric and asymmetric divisions. In addition we show that the balance between these divisions is not hardwired but responsive to extrinsic and intrinsic cues. Precursors in a prodifferentiation environment preferentially divide asymmetrically, whereas those in a prorenewal environment primarily divide symmetrically. Oncoproteins can also influence division pattern: although BCR-ABL predominantly alters the rate of division and death, NUP98-HOXA9 promotes symmetric division, suggesting that distinct oncogenes subvert different aspects of cellular function. These studies establish a system for tracking division of hematopoietic precursors and show that the balance of symmetric and asymmetric division can be influenced by the microenvironment and subverted by oncogenes.

AB - Stem cells are thought to balance self-renewal and differentiation through asymmetric and symmetric divisions, but whether such divisions occur during hematopoietic development remains unknown. Using a Notch reporter mouse, in which GFP acts as a sensor for differentiation, we image hematopoietic precursors and show that they undergo both symmetric and asymmetric divisions. In addition we show that the balance between these divisions is not hardwired but responsive to extrinsic and intrinsic cues. Precursors in a prodifferentiation environment preferentially divide asymmetrically, whereas those in a prorenewal environment primarily divide symmetrically. Oncoproteins can also influence division pattern: although BCR-ABL predominantly alters the rate of division and death, NUP98-HOXA9 promotes symmetric division, suggesting that distinct oncogenes subvert different aspects of cellular function. These studies establish a system for tracking division of hematopoietic precursors and show that the balance of symmetric and asymmetric division can be influenced by the microenvironment and subverted by oncogenes.

KW - STEMCELL

UR - http://www.scopus.com/inward/record.url?scp=35848948403&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=35848948403&partnerID=8YFLogxK

U2 - 10.1016/j.stem.2007.08.009

DO - 10.1016/j.stem.2007.08.009

M3 - Article

C2 - 18345353

AN - SCOPUS:35848948403

SN - 1934-5909

VL - 1

SP - 541

EP - 554

JO - Cell Stem Cell

JF - Cell Stem Cell

IS - 5

ER -

Imaging Hematopoietic Precursor Division in Real Time

Abstract

Bibliographical note

Keywords

Access

OpenUrl availability

Other files and links

Fingerprint

Cite this