A crucial role for the homeodomain transcription factor Hhex in lymphopoiesis

Jacob T. Jackson, Chayanica Nasa, Wei Shi, Nicholas D. Huntington, Clifford W. Bogue, Warren S. Alexander, Matthew P. McCormack

Research output: Contribution to journalArticleResearchpeer-review

16 Citations (Scopus)

Abstract

The hematopoietically expressed homeobox gene, Hhex, is a transcription factor that is important for development of definitive hematopoietic stem cells (HSCs) and B cells, and that causes T-cell leukemia when overexpressed. Here, we have used an Hhex inducible knockout mousemodel to study the role of Hhex in adult hematopoiesis. We found that loss of Hhex was tolerated in HSCs and myeloid lineages, but resulted in a progressive loss of B lymphocytes in the circulation. This was accompanied by a complete loss of B-cell progenitors in the bone marrow and of transitional B-cell subsets in the spleen. In addition, transplantation and in vitro culture experiments demonstrated an almost complete failure of Hhex-null HSCs to contribute to lymphoid lineages beyond the common lymphoid precursor stage, including T cells, B cells, NK cells, and dendritic cells. Gene expression analysis of Hhex-deleted progenitors demonstrated deregulated expression of a number of cell cycle regulators. Overexpression of one of these, cyclin D1, could rescue the B-cell developmental potential of Hhex-null lymphoid precursors. Thus, Hhex is a key regulator of early lymphoid development, functioning, at least in part, via regulation of the cell cycle.

Original languageEnglish
Pages (from-to)803-814
Number of pages12
JournalBlood
Volume125
Issue number5
DOIs
Publication statusPublished - 29 Jan 2015
Externally publishedYes

Cite this

Jackson, Jacob T. ; Nasa, Chayanica ; Shi, Wei ; Huntington, Nicholas D. ; Bogue, Clifford W. ; Alexander, Warren S. ; McCormack, Matthew P. / A crucial role for the homeodomain transcription factor Hhex in lymphopoiesis. In: Blood. 2015 ; Vol. 125, No. 5. pp. 803-814.
@article{2b293ec411e7459ba00619859ae3e617,
title = "A crucial role for the homeodomain transcription factor Hhex in lymphopoiesis",
abstract = "The hematopoietically expressed homeobox gene, Hhex, is a transcription factor that is important for development of definitive hematopoietic stem cells (HSCs) and B cells, and that causes T-cell leukemia when overexpressed. Here, we have used an Hhex inducible knockout mousemodel to study the role of Hhex in adult hematopoiesis. We found that loss of Hhex was tolerated in HSCs and myeloid lineages, but resulted in a progressive loss of B lymphocytes in the circulation. This was accompanied by a complete loss of B-cell progenitors in the bone marrow and of transitional B-cell subsets in the spleen. In addition, transplantation and in vitro culture experiments demonstrated an almost complete failure of Hhex-null HSCs to contribute to lymphoid lineages beyond the common lymphoid precursor stage, including T cells, B cells, NK cells, and dendritic cells. Gene expression analysis of Hhex-deleted progenitors demonstrated deregulated expression of a number of cell cycle regulators. Overexpression of one of these, cyclin D1, could rescue the B-cell developmental potential of Hhex-null lymphoid precursors. Thus, Hhex is a key regulator of early lymphoid development, functioning, at least in part, via regulation of the cell cycle.",
author = "Jackson, {Jacob T.} and Chayanica Nasa and Wei Shi and Huntington, {Nicholas D.} and Bogue, {Clifford W.} and Alexander, {Warren S.} and McCormack, {Matthew P.}",
year = "2015",
month = "1",
day = "29",
doi = "10.1182/blood-2014-06-579813",
language = "English",
volume = "125",
pages = "803--814",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "5",

}

A crucial role for the homeodomain transcription factor Hhex in lymphopoiesis. / Jackson, Jacob T.; Nasa, Chayanica; Shi, Wei; Huntington, Nicholas D.; Bogue, Clifford W.; Alexander, Warren S.; McCormack, Matthew P.

In: Blood, Vol. 125, No. 5, 29.01.2015, p. 803-814.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - A crucial role for the homeodomain transcription factor Hhex in lymphopoiesis

AU - Jackson, Jacob T.

AU - Nasa, Chayanica

AU - Shi, Wei

AU - Huntington, Nicholas D.

AU - Bogue, Clifford W.

AU - Alexander, Warren S.

AU - McCormack, Matthew P.

PY - 2015/1/29

Y1 - 2015/1/29

N2 - The hematopoietically expressed homeobox gene, Hhex, is a transcription factor that is important for development of definitive hematopoietic stem cells (HSCs) and B cells, and that causes T-cell leukemia when overexpressed. Here, we have used an Hhex inducible knockout mousemodel to study the role of Hhex in adult hematopoiesis. We found that loss of Hhex was tolerated in HSCs and myeloid lineages, but resulted in a progressive loss of B lymphocytes in the circulation. This was accompanied by a complete loss of B-cell progenitors in the bone marrow and of transitional B-cell subsets in the spleen. In addition, transplantation and in vitro culture experiments demonstrated an almost complete failure of Hhex-null HSCs to contribute to lymphoid lineages beyond the common lymphoid precursor stage, including T cells, B cells, NK cells, and dendritic cells. Gene expression analysis of Hhex-deleted progenitors demonstrated deregulated expression of a number of cell cycle regulators. Overexpression of one of these, cyclin D1, could rescue the B-cell developmental potential of Hhex-null lymphoid precursors. Thus, Hhex is a key regulator of early lymphoid development, functioning, at least in part, via regulation of the cell cycle.

AB - The hematopoietically expressed homeobox gene, Hhex, is a transcription factor that is important for development of definitive hematopoietic stem cells (HSCs) and B cells, and that causes T-cell leukemia when overexpressed. Here, we have used an Hhex inducible knockout mousemodel to study the role of Hhex in adult hematopoiesis. We found that loss of Hhex was tolerated in HSCs and myeloid lineages, but resulted in a progressive loss of B lymphocytes in the circulation. This was accompanied by a complete loss of B-cell progenitors in the bone marrow and of transitional B-cell subsets in the spleen. In addition, transplantation and in vitro culture experiments demonstrated an almost complete failure of Hhex-null HSCs to contribute to lymphoid lineages beyond the common lymphoid precursor stage, including T cells, B cells, NK cells, and dendritic cells. Gene expression analysis of Hhex-deleted progenitors demonstrated deregulated expression of a number of cell cycle regulators. Overexpression of one of these, cyclin D1, could rescue the B-cell developmental potential of Hhex-null lymphoid precursors. Thus, Hhex is a key regulator of early lymphoid development, functioning, at least in part, via regulation of the cell cycle.

UR - http://www.scopus.com/inward/record.url?scp=84921772623&partnerID=8YFLogxK

U2 - 10.1182/blood-2014-06-579813

DO - 10.1182/blood-2014-06-579813

M3 - Article

VL - 125

SP - 803

EP - 814

JO - Blood

JF - Blood

SN - 0006-4971

IS - 5

ER -