Stem cell networks

AbstractIn most organ systems, regeneration is a coordinated effort that involves many stem cells, but little is known about whether and how individual stem cells compensate for the functional deficiencies of other stem cells. Functional compensation between stem cells is critically important during disease progression and treatment. Here, we show how individual hematopoietic stem cells (HSCs) in a mouse heterogeneously compensate for the deficiencies of other HSCs’ during lymphopoiesis by increasing their clonal expansion at specific differentiation stages. This compensation rescues the overall blood supply and influences blood cell types outside of the deficient lineages in distinct patterns. We have identified the molecular regulators and signaling pathways in HSCs that are involved in this process. Our data demonstrate how stem cells interact with each other to constitute a coordinated network that is robust enough to withstand minor functional disruptions. Exploiting the innate compensation capacity of stem cell networks may improve the prognosis and treatment of many diseases.

Download Full-text

MET Expression and Cancer Stem Cell Networks Impact Outcome in High-Grade Serous Ovarian Cancer

Genes ◽

10.3390/genes12050742 ◽

2021 ◽

Vol 12 (5) ◽

pp. 742

Author(s):

Maria Bååth ◽

Jenny-Maria Jönsson ◽

Sofia Westbom Fremer ◽

Laura Martín de la Fuente ◽

Lena Tran ◽

...

Keyword(s):

Ovarian Cancer ◽

Stem Cell ◽

Cell Lines ◽

Synergistic Effects ◽

Combined Treatment ◽

Rank Test ◽

High Grade ◽

Cancer Types ◽

Cell Networks

Overexpression of the receptor tyrosine kinase MET has been linked to poor survival in several cancer types, and MET has been suggested to interact with stem cell networks. In vitro studies have further suggested a possible benefit of a combined treatment using PARP and MET inhibitors. We used a tissue microarray (TMA) with 130 samples of advanced-stage high-grade serous fallopian tube/ovarian cancer (HGSC) to investigate the prognostic value of MET protein expression alone and in combination with the stem cell factor SOX2. The possible synergistic effects of a PARP and MET inhibitor treatment were evaluated in two cell lines with BRCA1 or BRCA2 deficiency and in their BRCA1/2-proficient counterparts. Patients with tumors positive for MET had worse overall survival (log-rank test, p = 0.015) compared to patients with MET-negative tumors. The prognostic role of MET was even more prominent in the subgroup of patients with SOX2-negative tumors (p = 0.0081). No synergistic effects of the combined treatment with PARP and MET inhibitors were found in the cell lines examined. We conclude that MET expression could be used as a marker for OS in HGSC and that stemness should be taken into consideration when evaluating the mechanisms of this effect.

Download Full-text

Encyclopedia of Systems Biology ◽

10.1007/978-1-4419-9863-7_1577 ◽

2013 ◽

pp. 1987-1990

Author(s):

Eric Werner

Keyword(s):

Stem Cell ◽

Cell Networks

Download Full-text

Major Disruption of Bone Marrow Stromal Cell Networks and Persistent Loss of Hematopoietic Stem Cell Function upon Chronic Viral Infection

Experimental Hematology ◽

10.1016/j.exphem.2018.06.250 ◽

2018 ◽

Vol 64 ◽

pp. S73

Author(s):

Stephan Isringhausen ◽

Ute Suessbier ◽

Larisa Kovtonyuk ◽

Nike Kräutler ◽

Alvaro Gomariz-Carillo ◽

...

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Stromal Cell ◽

Cell Function ◽

Bone Marrow Stromal Cell ◽

Chronic Viral Infection ◽

Hematopoietic Stem ◽

Marrow Stromal Cell ◽

Major Disruption ◽

Cell Networks

Download Full-text

Analysis of phloem trajectory links tissue maturation to cell specialization

10.1101/2021.01.18.427084 ◽

2021 ◽

Author(s):

Pawel Roszak ◽

Jung-ok Heo ◽

Bernhard Blob ◽

Koichi Toyokura ◽

Maria Angels de Luis Balaguer ◽

...

Keyword(s):

Stem Cell ◽

Transcription Factors ◽

Stem Cell Niche ◽

Developmental Time ◽

Developmental Trajectory ◽

Arabidopsis Root ◽

Cell Type Specific ◽

Direct Target ◽

Cell Niche ◽

Cell Networks

AbstractThe mechanisms that allow cells in the plant meristem to coordinate tissue-wide maturation gradients with specialized cell networks are critical for indeterminate growth. Here, we reconstructed the protophloem developmental trajectory of 19 cells from cell birth to terminal differentiation at single cell resolution in the Arabidopsis root. We found that cellular specification is mediated near the stem cell niche by PHLOEM EARLY DOF (PEAR) transcription factors. However, the PEAR dependent differentiation program is repressed by a broad gradient of PLETHORA (PLT) transcription factors, which directly inhibit PEARs’ own direct target ALTERED PHLOEM DEVELOPMENT (APL). The dissipation of PLT gradient around 7 cells from the stem cell activates APL expression, and a subsequent transitional network that results in a “seesaw” pattern of mutual inhibition over developmental time. Together, we provide a mechanistic understanding of how morphogen-like maturation gradients interface with cell-type specific transcriptional regulators to stage cellular differentiation.

Download Full-text